Evaluation of rGH Therapy to Prevent Muscle Atrophy in Patients With ACL Tears

• Sponsor: University of Michigan (Other)
• Overall Status: Completed
• CT.gov ID: NCT02420353
• Collaborator: Hospital for Special Surgery, New York (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 41
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

Anterior cruciate ligament (ACL) tears are among the most frequent traumatic knee injuries that occur in physically active individuals. Despite advances in minimally invasive surgical reconstruction techniques and aggressive rehabilitation, this atrophy and loss of strength can persist even after patients return to full activity and can place them at considerable risk for re-injury and developing osteoarthritis (OA). The design of new therapeutic interventions to prevent muscle atrophy is needed to advance the care of patients who suffer from ACL injuries. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis plays an important role in promoting muscle growth and protecting muscle from atrophy. While GH therapy has shown promise in protecting immobilized muscle from various models of disuse atrophy, it remains unknown whether GH can help to restore strength and protect against the loss in strength that occurs after ACL tear. GH therapy may help to accelerate the safe return to play of patients that suffer ACL tears, and help to prevent the long-term OA and reduction in quality of life that occur after these traumatic knee injuries.

Condition or Disease	Intervention/Treatment	Phase
Rupture of Anterior Cruciate Ligament	Drug: Somatropin; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Evaluation of Recombinant Growth Hormone Therapy to Prevent Muscle Atrophy in Patients With Anterior Cruciate Ligament Tears
• Actual Study Start Date: May 1, 2015
• Actual Primary Completion Date: Oct 1, 2018
• Actual Study Completion Date: Oct 1, 2018

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Somatropin Somatropin of rDNA origin	Drug: Somatropin; GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.
Placebo Comparator: Placebo A placebo vehicle that contains somatropin diluent but no active hormone.	Drug: Placebo; A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.

Outcome Measures

Primary Outcome Measures

1. Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op [at 26 wks post-op]

   Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

Secondary Outcome Measures

1. Normative Isokinetic Extension (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

   Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

2. Normative Isokinetic Flexion (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

   Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

3. Normative Isokinetic Flexion (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

   Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

4. Normative Isometric Extension (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

   Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

5. Normative Isometric Extension (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

   Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

6. Normative Isometric Flexion (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

   Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

7. Normative Isometric Flexion (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

   Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.

8. Absolute Isokinetic Extension (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

   Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.

9. Absolute Isokinetic Extension (Nm) at 26 wk Post-op [at 26 wk post-op]

   Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.

10. Absolute Isokinetic Flexion (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

    Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.

11. Absolute Isokinetic Flexion (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

    Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.

12. Absolute Isometric Extension (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

    Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.

13. Absolute Isometric Extension (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

    Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.

14. Absolute Isometric Flexion (Nm) at Pre-op (Baseline) [at pre-op (baseline)]

    Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.

15. Absolute Isometric Flexion (Nm) at 26 Weeks Post-op [at 26 weeks post-op]

    Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.

16. VR12 Health Survey: Physical Health Summary Measure Score at Pre-op (Baseline) [at pre-op (baseline)]

    The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.

17. VR12 Health Survey: Physical Health Summary Measure Score at 26 Weeks Post-op [at 26 weeks post-op]

    The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.

18. VR12 Health Survey: Mental Health Summary Measure Score at Pre-op (Baseline) [at pre-op (baseline)]

    The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.

19. VR12 Health Survey: Mental Health Summary Measure Score at 26 Weeks Post-op [at 26 weeks post-op]

    The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.

20. International Knee Document Committee (IKDC) at Pre-op (Baseline) [at pre-op (baseline)]

    The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.

21. International Knee Documentation Committee (IKDC) up to 26 wk Post-op [up to 26 wk post-op]

    The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.

22. The Knee Injury and Osteoarthritis Outcome Score (KOOS): Patient Reported Outcome Measure: ADL at 26 Weeks Post-op [at 26 weeks post-op]

    KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

23. KOOS Patient Reported Outcome Measure: ADL at Pre-op (Baseline) [at pre-op (baseline)]

    KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

24. KOOS Patient Reported Outcome Measure: Pain at 26 Weeks Post-op [at 26 weeks post-op]

    KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

25. KOOS Patient Reported Outcome Measure: Pain at Pre-op (Baseline) [at pre-op (baseline)]

    KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

26. KOOS Patient Reported Outcome Measure: Quality of Life at 26 Weeks Post-op [at 26 weeks post-op]

    KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

27. KOOS Patient Reported Outcome Measure: Quality of Life at Pre-op (Baseline) [at pre-op (baseline)]

    KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

28. KOOS Patient Reported Outcome Measure: Sport and Recreation at 26 Weeks Post-op [at 26 weeks post-op]

    KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.

29. KOOS Patient Reported Outcome Measure: Sports and Recreation at Pre-op (Baseline) [at pre-op (baseline)]

    KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.

30. KOOS Patient Reported Outcome Measure: Symptoms at 26 Weeks Post-op [at 26 weeks post-op]

    KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

31. KOOS Patient Reported Outcome Measure: Symptoms at Pre-op (Baseline) [at pre-op (baseline)]

    KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures

32. Absolute Quadriceps Volume (L) at Pre-op (Baseline) [at pre-op (baseline)]

    Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

33. Absolute Quadricep Volume (L) at 26 Week Post-op [at 26 week post-op]

    Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

34. Absolute Hamstring Volume (L) at Pre-op (Baseline) [at pre-op (baseline)]

    Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

35. Absolute Hamstring Volume (L) at 26 Weeks Post-op [at 26 weeks post-op]

    Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

36. Normalized Quadriceps Volume (L) at Pre-op (Baseline) [at pre-op (baseline)]

    Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

37. Normalized Quadriceps Volume (L) at 26 Weeks Post-op [at 26 weeks post-op]

    Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

38. Normalized Hamstring Volume (L) at Pre-op (Baseline) [at pre-op (baseline)]

    Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

39. Normalized Hamstring Volume (L) at 26 Weeks Post-op [at 26 weeks post-op]

    Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).

40. Insulin Like Growth Factor (IGF1) at -1 and 5 Weeks Post-op [Area under the curve between -1 and 5 weeks post-op]

    IGF1 was measured from serum using an IMMULITE 2000 system (Siemens).

41. Myostatin at -1 and 5 Weeks Post-op [Area under the curve between -1 and 5 weeks post-op]

    Myostatin was measured from plasma using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.

42. MMP3 at -1 and 5 Weeks Post-op [Area under the curve between -1 and 5 weeks post-op]

    Matrix metalloproteinase-3 (MMP3) was measured from serum using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.

43. Hyaluronic Acid at -1 and 5 Weeks Post-op [Area under the curve between -1 and 5 weeks post-op]

    Hyaluronic acid was measured from plasma using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Males between the ages of 18 and 35

• Have acute unilateral complete ACL tears with or without bucket handle medial meniscus tears that occurred within the past 6 months

• Consent to undergo an ACL reconstruction by an orthopaedic surgeon using a patellar tendon or hamstring autograft

• Will be performing supervised post-operative rehabilitation at UMHS MedSport at Dominos Farms

Exclusion Criteria:

• Patients who are undergoing a revision ACL reconstruction

• Had a previous injury to the involved knee

• Have an allergy to recombinant GH

• Have a BMI<20 or >35

• Have a growth disorder of bones or connective tissue, type 1 diabetes mellitus, type 2 diabetes mellitus, or who have a history of carpal tunnel syndrome, trigger finger, myopathy, cancer, endocrine disorder, hypertension or rheumatologic disorder.

• Systolic blood pressure >140mm Hg or diastolic blood pressure >90mm Hg, or with resting heart rate >110 BPM or <40 BPM at screening.

• Additionally, because GH is currently listed as a banned substance by the World Anti-Doping Agency (WADA), National Collegiate Athletics Association (NCAA) and most professional sports agencies, we will exclude patients who are current collegiate, professional or elite athletes.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Michigan	Ann Arbor	Michigan	United States	48109

Sponsors and Collaborators

• University of Michigan
• Hospital for Special Surgery, New York

Investigators

• Principal Investigator: Christopher L Mendias, PhD, ATC, University of Michigan

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Sep 24, 2019

More Information

Publications

• Boesen AP, Dideriksen K, Couppé C, Magnusson SP, Schjerling P, Boesen M, Kjaer M, Langberg H. Tendon and skeletal muscle matrix gene expression and functional responses to immobilisation and rehabilitation in young males: effect of growth hormone administration. J Physiol. 2013 Dec 1;591(23):6039-52. doi: 10.1113/jphysiol.2013.261263. Epub 2013 Sep 30.
• Gelato M, McNurlan M, Freedland E. Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment. Clin Ther. 2007 Nov;29(11):2269-88. Review.
• Mendias CL, Lynch EB, Davis ME, Sibilsky Enselman ER, Harning JA, Dewolf PD, Makki TA, Bedi A. Changes in circulating biomarkers of muscle atrophy, inflammation, and cartilage turnover in patients undergoing anterior cruciate ligament reconstruction and rehabilitation. Am J Sports Med. 2013 Aug;41(8):1819-26. doi: 10.1177/0363546513490651. Epub 2013 Jun 5.
• Surya S, Horowitz JF, Goldenberg N, Sakharova A, Harber M, Cornford AS, Symons K, Barkan AL. The pattern of growth hormone delivery to peripheral tissues determines insulin-like growth factor-1 and lipolytic responses in obese subjects. J Clin Endocrinol Metab. 2009 Aug;94(8):2828-34. doi: 10.1210/jc.2009-0638. Epub 2009 May 26.

• Responsible Party: Christopher Mendias, PhD, ATC, Associate Professor, University of Michigan
• ClinicalTrials.gov Identifier: NCT02420353
• Other Study ID Numbers: HUM00087702; IND Exemption 123189
• First Posted: Apr 17, 2015
• Last Update Posted: Jan 6, 2020
• Last Verified: Dec 1, 2019

• Keywords provided by Christopher Mendias, PhD, ATC, Associate Professor, University of Michigan: muscle atrophy; growth hormone; ACL tear
• Additional relevant MeSH terms: Muscular Atrophy; Atrophy; Rupture

Study Results

Participant Flow

Recruitment Details	Recruitment completed at the University of Michigan Sports Medicine Clinic

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Period Title: Overall Study
STARTED	10	10
Allocation to Intervention	10	10
COMPLETED	10	9
NOT COMPLETED	0	1

Baseline Characteristics

Arm/Group Title	Somatropin	Placebo	Total
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.	Total of all reporting groups
Overall Participants	10	9	19
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	10 100%	9 100%	19 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	10 100%	9 100%	19 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Isokinetic Knee Strength (Nm) (Newton Meters) [Mean (Standard Deviation) ]
Absolute Isokinetic Flexion 60 dg/s Surgical	74.7 (27.9)	77.5 (11.4)	76.0 (21.2)
Absolute Isokinetic Extension 60 dg/s Surgical	127.9 (46.7)	124.7 (43.1)	126.3 (43.8)

Outcome Measures

1. Primary Outcome

Title	Normative Isokinetic Knee Extension Strength, Measured in Newton Meters (Nm) at 26 Weeks Post-op
Description	Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 wks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.881	0.681

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments	Mixed effect model
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0498
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Normative Isokinetic Extension (Nm) at Pre-op (Baseline)
Description	Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.746	0.816

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects model
Statistical Test of Hypothesis	p-Value	0.7024
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Normative Isokinetic Flexion (Nm) at Pre-op (Baseline)
Description	Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.738	0.92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects model
Statistical Test of Hypothesis	p-Value	0.135
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Normative Isokinetic Flexion (Nm) at 26 Weeks Post-op
Description	Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then normalized to the participants nonsurgical limb.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	1.068	1.028

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects model
Statistical Test of Hypothesis	p-Value	0.6836
	Comments
	Method	Mixed Models Analysis
	Comments

5. Secondary Outcome

Title	Normative Isometric Extension (Nm) at Pre-op (Baseline)
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.761	0.778

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.9271
	Comments
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Normative Isometric Extension (Nm) at 26 Weeks Post-op
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then normalized to the participants nonsurgical limb.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.718	0.633

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.1576
	Comments
	Method	Mixed Models Analysis
	Comments

7. Secondary Outcome

Title	Normative Isometric Flexion (Nm) at Pre-op (Baseline)
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	0.771	0.867

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.5586
	Comments
	Method	Mixed Models Analysis
	Comments

8. Secondary Outcome

Title	Normative Isometric Flexion (Nm) at 26 Weeks Post-op
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Normalized values were calculated by dividing the value from the injured limb by the value from the contralateral, uninjured leg prior to surgery. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then normalized to the participants nonsurgical limb.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	1.017	0.954

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	Mixed Models Analysis
	Comments

9. Secondary Outcome

Title	Absolute Isokinetic Extension (Nm) at Pre-op (Baseline)
Description	Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	127.9	124.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.8573
	Comments
	Method	Mixed Models Analysis
	Comments

10. Secondary Outcome

Title	Absolute Isokinetic Extension (Nm) at 26 wk Post-op
Description	Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 wk post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	140.1	105.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0564
	Comments
	Method	Mixed Models Analysis
	Comments

11. Secondary Outcome

Title	Absolute Isokinetic Flexion (Nm) at Pre-op (Baseline)
Description	Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isokinetic knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	74.7	77.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.7883
	Comments
	Method	Mixed Models Analysis
	Comments

12. Secondary Outcome

Title	Absolute Isokinetic Flexion (Nm) at 26 Weeks Post-op
Description	Absolute Isokinetic knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isokinetic measurements were performed at a speed of 60º/sec from a range of 0º to 90º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	103.9	86.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0901
	Comments
	Method	Mixed Models Analysis
	Comments

13. Secondary Outcome

Title	Absolute Isometric Extension (Nm) at Pre-op (Baseline)
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	183.1	172.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.6292
	Comments
	Method	Mixed Models Analysis
	Comments

14. Secondary Outcome

Title	Absolute Isometric Extension (Nm) at 26 Weeks Post-op
Description	Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	172.4	140.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.161
	Comments
	Method	Mixed Models Analysis
	Comments

15. Secondary Outcome

Title	Absolute Isometric Flexion (Nm) at Pre-op (Baseline)
Description	Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm).

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	69.2	77.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.4437
	Comments
	Method	Mixed Models Analysis
	Comments

16. Secondary Outcome

Title	Absolute Isometric Flexion (Nm) at 26 Weeks Post-op
Description	Absolute Isometric knee flexion and extension strength measurements were obtained in a System 3 dynamometer (BioDex, Shirley, New York). Isometric measurements were performed at 45º of knee flexion. Strength values were calculated by comparing the affected limb of each subject across study group. For each measurement, the highest force from a series of 5 repetitions was used.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were analyzed for bilateral isometric knee strength using the BioDex system 3 results where recorded in newton meters (Nm), results where then compared between study groups.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Nm]	84.6	88.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.7325
	Comments
	Method	Mixed Models Analysis
	Comments

17. Secondary Outcome

Title	VR12 Health Survey: Physical Health Summary Measure Score at Pre-op (Baseline)
Description	The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the VR12 survey, this 12 part questionnaire is then score in two parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [T-score]	46.5	45.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.6291
	Comments
	Method	Mixed Models Analysis
	Comments

18. Secondary Outcome

Title	VR12 Health Survey: Physical Health Summary Measure Score at 26 Weeks Post-op
Description	The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed PCS maximum: 72.11; minimum: 0.59.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the VR12 survey, this 12 part questionnaire is then score in two parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [T-score]	52.9	50.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed-effects model
Statistical Test of Hypothesis	p-Value	0.3332
	Comments
	Method	Mixed Models Analysis
	Comments

19. Secondary Outcome

Title	VR12 Health Survey: Mental Health Summary Measure Score at Pre-op (Baseline)
Description	The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the VR12 survey, this 12 part questionnaire is then score in two parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [T-score]	54.6	55.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.79
	Comments
	Method	Mixed Models Analysis
	Comments

20. Secondary Outcome

Title	VR12 Health Survey: Mental Health Summary Measure Score at 26 Weeks Post-op
Description	The VR-12 includes 12 questions that do not give an overall score but yield a physical and mental component score. PCS and MCS summary scores are standardized using a t-score transformation and normalized to the U.S. population of a score of 50 and a standard deviation of 10. Higher PCS and MCS scores indicate better health. Medical Expenditure Panel Survey (MEPS) collected between 2000 and 2002 standard norms range as followed MCS Maximum: 76.09; Minimum: -2.47.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the VR12 survey, this 12 part questionnaire is then score in two parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [T-score]	56.7	59.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.4965
	Comments
	Method	Mixed Models Analysis
	Comments

21. Secondary Outcome

Title	International Knee Document Committee (IKDC) at Pre-op (Baseline)
Description	The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants complete the IKDC outcome measure, the form was administer by hand at the time of the study visits for each study timepoint.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	54.6	55.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.1331
	Comments
	Method	Mixed Models Analysis
	Comments

22. Secondary Outcome

Title	International Knee Documentation Committee (IKDC) up to 26 wk Post-op
Description	The IKDC percentage score is a subjective patients reported outcome measure (PROM) that scores a participants over all score. The PROM looks at 3 categories: symptoms, sports activity, and knee function. Scores range from 0 to 100, the final score given is interpreted as a measure of function with higher scores representing higher levels of function.
Time Frame	up to 26 wk post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants complete the IKDC outcome measure, the form was administer by hand at the time of the study visits for each study timepoint.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [units on a scale]	65	67

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed-model analysis
Statistical Test of Hypothesis	p-Value	0.5251
	Comments
	Method	Mixed Models Analysis
	Comments

23. Secondary Outcome

Title	The Knee Injury and Osteoarthritis Outcome Score (KOOS): Patient Reported Outcome Measure: ADL at 26 Weeks Post-op
Description	KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	98	98.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.1064
	Comments
	Method	Mixed Models Analysis
	Comments

24. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: ADL at Pre-op (Baseline)
Description	KOOS Function in daily living (ADL) (17 items). A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	88	91

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.4852
	Comments
	Method	Mixed Models Analysis
	Comments

25. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Pain at 26 Weeks Post-op
Description	KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	91	92

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.7943
	Comments
	Method	Mixed Models Analysis
	Comments

26. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Pain at Pre-op (Baseline)
Description	KOOS Pain (9 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	74	83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0894
	Comments
	Method	Mixed Models Analysis
	Comments

27. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Quality of Life at 26 Weeks Post-op
Description	KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	53	63

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.0673
	Comments
	Method	Mixed Models Analysis
	Comments

28. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Quality of Life at Pre-op (Baseline)
Description	KOOS Quality of Life (QoL) (4 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	33	47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.0185
	Comments
	Method	Mixed Models Analysis
	Comments

29. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Sport and Recreation at 26 Weeks Post-op
Description	KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	67.5	72.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.6094
	Comments
	Method	Mixed Models Analysis
	Comments

30. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Sports and Recreation at Pre-op (Baseline)
Description	KOOS Sport and Recreation (Sport/Rec) (5 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures.
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	46.5	55.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.3279
	Comments
	Method	Mixed Models Analysis
	Comments

31. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Symptoms at 26 Weeks Post-op
Description	KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	60	68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.2802
	Comments
	Method	Mixed Models Analysis
	Comments

32. Secondary Outcome

Title	KOOS Patient Reported Outcome Measure: Symptoms at Pre-op (Baseline)
Description	KOOS Symptoms (7 items) A Likert scale is used and all items have five possible answer options scored from 0 (No Problems) to 4 (Extreme Problems) and each of the five scores is calculated as the sum of the items included. An aggregate total score is not calculated since it is regarded desirable to analyze and interpret the five dimensions separately. Maximum score 100% / Minimum score 0%. Scores are transformed to a 0-100 scale, with zero representing extreme knee problems and 100 representing no knee problems as is common in orthopaedic assessment scales and generic measures
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

A total of 19 participants were administered the KOOS survey, this 42 part questionnaire is then score in five parts based on the answers selected by the subjects.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [score on a scale]	53	64

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.1064
	Comments
	Method	Mixed Models Analysis
	Comments

33. Secondary Outcome

Title	Absolute Quadriceps Volume (L) at Pre-op (Baseline)
Description	Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	2.48	2.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0509
	Comments
	Method	Mixed Models Analysis
	Comments

34. Secondary Outcome

Title	Absolute Quadricep Volume (L) at 26 Week Post-op
Description	Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at 26 week post-op

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	2.27	2.12

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects analysis
Statistical Test of Hypothesis	p-Value	0.1605
	Comments
	Method	Mixed Models Analysis
	Comments

35. Secondary Outcome

Title	Absolute Hamstring Volume (L) at Pre-op (Baseline)
Description	Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	1	0.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0357
	Comments
	Method	Mixed Models Analysis
	Comments

36. Secondary Outcome

Title	Absolute Hamstring Volume (L) at 26 Weeks Post-op
Description	Bilateral MRI scans were obtained at specific time points to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	0.98	0.88

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0122
	Comments
	Method	Mixed Models Analysis
	Comments

37. Secondary Outcome

Title	Normalized Quadriceps Volume (L) at Pre-op (Baseline)
Description	Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	1	0.85

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.5853
	Comments
	Method	Mixed Models Analysis
	Comments

38. Secondary Outcome

Title	Normalized Quadriceps Volume (L) at 26 Weeks Post-op
Description	Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	0.91	0.85

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.6288
	Comments
	Method	Mixed Models Analysis
	Comments

39. Secondary Outcome

Title	Normalized Hamstring Volume (L) at Pre-op (Baseline)
Description	Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at pre-op (baseline)

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	1.06	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.5022
	Comments
	Method	Mixed Models Analysis
	Comments

40. Secondary Outcome

Title	Normalized Hamstring Volume (L) at 26 Weeks Post-op
Description	Normalized volume relative to the pre-op measurements of the uninjured limb, used to assess the muscle volume of the quadriceps and hamstring muscle groups will be calculated using GE ImagePACS software (FDA cleared software which is the standard software used to read and analyze imaging studies in the UMHS).
Time Frame	at 26 weeks post-op

Outcome Measure Data

Analysis Population Description

Scans were performed on a total of 19 participant at three time points throughout the study.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [Liters]	1.03	0.93

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.7507
	Comments
	Method	Mixed Models Analysis
	Comments

41. Secondary Outcome

Title	Insulin Like Growth Factor (IGF1) at -1 and 5 Weeks Post-op
Description	IGF1 was measured from serum using an IMMULITE 2000 system (Siemens).
Time Frame	Area under the curve between -1 and 5 weeks post-op

Outcome Measure Data

Analysis Population Description

Blood was drawn from the antecubital vein from each patient at specific time points, plasma and serum were prepared from whole blood and stored at -80ºC.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [ng*days/mL]	22478	10626

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	<.0001
	Comments
	Method	Mixed Models Analysis
	Comments

42. Secondary Outcome

Title	Myostatin at -1 and 5 Weeks Post-op
Description	Myostatin was measured from plasma using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.
Time Frame	Area under the curve between -1 and 5 weeks post-op

Outcome Measure Data

Analysis Population Description

Blood was drawn from the antecubital vein from each patient at specific time points, plasma and serum were prepared from whole blood and stored at -80ºC.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [ng*days/mL]	190.7	193.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.8581
	Comments
	Method	Mixed Models Analysis
	Comments

43. Secondary Outcome

Title	MMP3 at -1 and 5 Weeks Post-op
Description	Matrix metalloproteinase-3 (MMP3) was measured from serum using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.
Time Frame	Area under the curve between -1 and 5 weeks post-op

Outcome Measure Data

Analysis Population Description

Blood was drawn from the antecubital vein from each patient at specific time points, plasma and serum were prepared from whole blood and stored at -80ºC.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [ng*days/mL]	1188	766

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	mixed effects model
Statistical Test of Hypothesis	p-Value	0.0208
	Comments
	Method	Mixed Models Analysis
	Comments

44. Secondary Outcome

Title	Hyaluronic Acid at -1 and 5 Weeks Post-op
Description	Hyaluronic acid was measured from plasma using ELISAs (R&D Systems, Minneapolis, MN) following manufacturer recommendations.
Time Frame	Area under the curve between -1 and 5 weeks post-op

Outcome Measure Data

Analysis Population Description

Blood was drawn from the antecubital vein from each patient at specific time points, plasma and serum were prepared from whole blood and stored at -80ºC.

Arm/Group Title	Somatropin	Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.	A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
Measure Participants	10	9
Mean (90% Confidence Interval) [ng*days/mL]	190.7	193.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Somatropin, Placebo
	Comments
	Type of Statistical Test	Other
	Comments	Mixed effects model
Statistical Test of Hypothesis	p-Value	0.8581
	Comments
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	1-3 weeks pre-op to 25 weeks post-op
Adverse Event Reporting Description	Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
Arm/Group Title	Somatropin		Placebo
Arm/Group Description	Somatropin of rDNA origin Somatropin: GH dose will be calculated by nomogram estimation of body surface area, and will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin GH treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take GH, but otherwise patients will take GH every day over this 6 week period.		A placebo vehicle that contains somatropin diluent but no active hormone. Placebo: A placebo diluent that will be administered via subcutaneous injection in the abdominal area twice per day (BID) at a dose of the equivalent concentration of 0.5mg GH per body surface area (BSA) in m2 (0.5mg/m2). Patients will begin treatment one week prior to surgery and will continue through 5 weeks after surgery. On the day of surgery, patients will not take medication, but otherwise patients will take medication every day over this 6 week period.
All Cause Mortality
	Somatropin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Serious Adverse Events
	Somatropin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/10 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Somatropin		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/10 (50%)		5/9 (55.6%)
Blood and lymphatic system disorders
Increased sweating	3/10 (30%)	3	2/9 (22.2%)	2
Gastrointestinal disorders
Constipation	1/10 (10%)	1	0/9 (0%)	0
General disorders
Back pain	5/10 (50%)	5	5/9 (55.6%)	5
Headache	3/10 (30%)	3	3/9 (33.3%)	3
Tingling sensation/numbness	2/10 (20%)	2	1/9 (11.1%)	1
Elevated alanine aminotransferase	2/10 (20%)	2	3/9 (33.3%)	3
Elevated aspirate aminotransferase	2/10 (20%)	2	3/9 (33.3%)	3
Temperature sensation fluctuations	1/10 (10%)	1	0/9 (0%)	0
Reduced appetite	1/10 (10%)	1	0/9 (0%)	0
Elevated blood glucose	0/10 (0%)	0	1/9 (11.1%)	1
Injection site bruising	0/10 (0%)	0	1/9 (11.1%)	1
Musculoskeletal and connective tissue disorders
Fatigue	4/10 (40%)	4	4/9 (44.4%)	4
Joint pain (other than surgical knee)	3/10 (30%)	3	2/9 (22.2%)	2
Muscle spasms/cramps	1/10 (10%)	1	0/9 (0%)	0
Psychiatric disorders
Insomnia	1/10 (10%)	1	0/9 (0%)	0

Limitations/Caveats

Please consult the full manuscript or contact the study PI for any questions about study results. Additional clinical trials must be conducted before definitive conclusions can be made.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.