TACL: Testosterone Administration and ACL Reconstruction in Men

• Sponsor: University of Southern California (Other)
• Overall Status: Completed
• CT.gov ID: NCT01595581
• Collaborator: Boston University (Other), University of Oregon (Other)
• Enrollment: 14
• Location: 1
• Arms: 2
• Duration (Months): 37
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study is being done to test whether taking testosterone can prevent loss of muscle mass and strength due to anterior cruciate ligament (ACL) reconstructive surgery. Testosterone is the principal male sex hormone and an anabolic (muscle promoting) steroid. It is essential for the development of male reproductive tissues and promotes increased muscle, bone mass, and the growth of body hair.

The investigators hope to learn whether testosterone given before and after ACL reconstructive surgery will increase muscle mass and strength and potentially improve recovery time following surgery.

Condition or Disease	Intervention/Treatment	Phase
Muscle Atrophy; ACL Reconstruction; Trauma; Osteoarthritis	Drug: Testosterone; Drug: Placebo	Phase 3

Detailed Description

Overall Objective: The overall objective of this study is to determine if 8 weeks of testosterone first administered 2 weeks prior to surgery, can improve the outcome of anterior cruciate ligament (ACL) reconstruction.

Overall Hypothesis: Standard-of-care rehabilitation with the addition of testosterone administration will augment muscle mass, strength, and physical function following ACL reconstructive surgery compared to standard rehabilitation alone.

Significance: Muscle mass and strength are greatly reduced following ACL surgery. The investigators hypothesize that administration of testosterone will minimize these reductions or potentially increase muscle mass and strength. In doing so, testosterone may hasten a patient's return to physical activity. If testosterone improves recovery after ACL surgery, the same treatment may be used for other injuries that involve trauma and muscle atrophy. Furthermore, this study will examine the effect of trauma with or without testosterone on myogenic regulators in muscle tissue taken during ACL surgery-providing possible mechanistic insights for the clinical outcomes.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Effects of Acute Testosterone Administration in Men on Muscle Mass, Strength, and Physical Function Following ACL Reconstructive Surgery
• Study Start Date: Apr 1, 2012
• Actual Primary Completion Date: May 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Testosterone Weekly injection of testosterone enanthate 200mg	Drug: Testosterone; 8 weeks of testosterone administration beginning 2 weeks before ACL surgery; Other Names: testosterone enanthate
Placebo Comparator: Placebo Weekly injection of saline as the placebo	Drug: Placebo; 8 weeks of saline administration beginning 2 weeks before ACL surgery; Other Names: saline

Outcome Measures

Primary Outcome Measures

1. Changes in Lean Mass [6, 12, and 24 weeks post operative]

   Relative changes in lean mass from 2 weeks prior to surgery to 6 weeks, 12 weeks, and 24 weeks following surgery between the two groups.

Secondary Outcome Measures

1. KOOS Scores [6 weeks, 12 weeks, 24 weeks post surgery]

   Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) from 2 weeks prior to surgery to 6, 12, and 24 weeks post surgery. KOOS is scored from 0 to 100 with 0 representing extreme knee problems and 100 representing normal knee function.

2. Strength [6, 12, and 24 weeks post surgery]

   Changes in muscle strength from the start of rehabilitation to 6, 12, and 24 weeks following surgery between the two groups in the injured limb.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 50 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• A complete ACL tear as visualized on MRI

• The ACL injury can be either "isolated" or combined with one or several of the following injuries visualized on MRI and/or arthroscopy:

• a meniscus tear that is either left untreated or treated with a partial resection

• a small, stable meniscus tear treated with fixation, but with the fixation not interfering with the rehabilitation protocol

• cartilage changes verified on MRI with an arthroscopically determined intact surface.

• A radiographic examination with normal joint status or combined with either one of the following findings:

• a small-avulsed fragment located laterally, usually described as a Segond fracture, JSN grade 1 or osteophytes grade 1 as determined by the OARSI atlas15

Exclusion Criteria:

• Previous major knee injury or knee surgery

• Associated posterior cruciate ligament (PCL) or medical collateral ligament (MCL) injury grade III

• Concomitant severe injury to contra-lateral knee

• Injury to the lateral/posterolateral ligament complex with significantly increased laxity

• Unstable longitudinal meniscus tear that requires repair and where the following postoperative treatment (we.e. bracing and limited range of motion) interferes with the rehabilitation protocol

• Bi-compartmental extensive meniscus resections

• Cartilage injury representing a full thickness loss down to bone

• Total rupture of MCL/LCL as visualized on MRI.

• History of deep vein thrombosis (DVT) or a disorder of the coagulative system

• Claustrophobia

• Prior or current use of anabolic steroids

• General systemic disease affecting physical function

• Chromosomal disorders

• Medications that interfere with testosterone production or function, including but not limited to 5α-reductase inhibitors

• Any other condition or treatment interfering with the completion of the trial

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033

Sponsors and Collaborators

• University of Southern California
• Boston University
• University of Oregon

Investigators

• Principal Investigator: Todd Schroeder, PhD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Todd Schroeder, Assistant Professor of Clinical Physical Therapy, University of Southern California
• ClinicalTrials.gov Identifier: NCT01595581
• Other Study ID Numbers: HS-11-00649
• First Posted: May 10, 2012
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Todd Schroeder, Assistant Professor of Clinical Physical Therapy, University of Southern California: Testosterone; ACL Reconstruction; Clinical outcomes; Lean mass; Strength; Muscle atrophy
• Additional relevant MeSH terms: Muscular Atrophy; Atrophy; Methyltestosterone; Testosterone; Testosterone undecanoate; Testosterone enanthate; Testosterone 17 beta-cypionate

Study Results

Participant Flow

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone: 8 weeks supraphysiologic dose testosterone enanthate	Saline: Placebo for 8 weeks
Period Title: Overall Study
STARTED	7	7
COMPLETED	6	7
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Testosterone	Placebo	Total
Arm/Group Description	Testosterone: 8 weeks 200mg dose testosterone enanthate	Saline: Placebo for 8 weeks	Total of all reporting groups
Overall Participants	7	7	14
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	7 100%	7 100%	14 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.4 (9.3)	26.2 (4.1)	28.2 (6.7)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	7 100%	7 100%	14 100%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	7 100%	7 100%	14 100%

Outcome Measures

1. Primary Outcome

Title	Changes in Lean Mass
Description	Relative changes in lean mass from 2 weeks prior to surgery to 6 weeks, 12 weeks, and 24 weeks following surgery between the two groups.
Time Frame	6, 12, and 24 weeks post operative

Outcome Measure Data

Analysis Population Description

Region of enrollment from the Los Angeles area.

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone: 8 weeks supraphysiologic dose testosterone enanthate. Ethnicity: 4 White, 2 Asian, 1 Black	Saline: Placebo for 8 weeks Ethnicity: 4 White, 1 Asian, 2 Hispanic
Measure Participants	6	7
6 weeks post op	2.8 (1.7)	-0.1 (1.5)
12 weeks post op	2.16 (3.48)	0.01 (1.08)
24 weeks post op	2.13 (5.3)	1.05 (1.18)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Testosterone, Placebo
	Comments	Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated. This statistical analysis applies to lean mass in participants 6 weeks post operative.
	Type of Statistical Test	Other
	Comments	Mann-Whitney U test for continuous variables and Fisher exact test for categorical variables
Statistical Test of Hypothesis	p-Value	0.35
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.9
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 1.5
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Testosterone, Placebo
	Comments	Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated. This statistical analysis applies to lean mass in participants 12 weeks post operative.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.48
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	2.17
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 2
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Testosterone, Placebo
	Comments	Power was estimated for change in lean mass of 3.0 plus or minus 1.5 kg in healthy men receiving testosterone. Using a significance level of 0.05 and a power of 0.80, a sample size of 6 participants per group was calculated. This statistical analysis applies to lean mass in participants 24 weeks post operative.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.74
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.08
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 15
	Estimation Comments

2. Secondary Outcome

Title	KOOS Scores
Description	Change in Knee Injury and Osteoarthritis Outcome Score (KOOS) from 2 weeks prior to surgery to 6, 12, and 24 weeks post surgery. KOOS is scored from 0 to 100 with 0 representing extreme knee problems and 100 representing normal knee function.
Time Frame	6 weeks, 12 weeks, 24 weeks post surgery

Outcome Measure Data

Analysis Population Description

Region of enrollment from the Los Angeles area.

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone: 8 weeks supraphysiologic dose testosterone enanthate	Saline: Placebo for 8 weeks
Measure Participants	6	7
6 weeks post op	63.2 (10.6)	65.5 (13)
12 weeks post op	76.7 (9.9)	73.2 (15)
24 weeks post op	84 (9.4)	86.6 (8.3)

3. Secondary Outcome

Title	Strength
Description	Changes in muscle strength from the start of rehabilitation to 6, 12, and 24 weeks following surgery between the two groups in the injured limb.
Time Frame	6, 12, and 24 weeks post surgery

Outcome Measure Data

Analysis Population Description

Region of enrollment from the Los Angeles area.

Arm/Group Title	Testosterone	Placebo
Arm/Group Description	Testosterone: 8 weeks supraphysiologic dose testosterone enanthate	Saline: Placebo for 8 weeks
Measure Participants	6	7
6 weeks post op	-53.5 (35.8)	-33.4 (37.4)
12 weeks post op	-18.3 (52.7)	-6.6 (40.3)
24 weeks post op	19.2 (60.9)	19.0 (33.9)

Adverse Events

Time Frame	Trough the study completion (24-weeks).
Adverse Event Reporting Description	All subjects were monitored/assessed for adverse events.
Arm/Group Title	Testosterone		Placebo
Arm/Group Description	Testosterone: 8 weeks supraphysiologic dose testosterone enanthate		Saline: Placebo for 8 weeks
All Cause Mortality
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)
Serious Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)
Other (Not Including Serious) Adverse Events
	Testosterone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/7 (0%)		0/7 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.