AAA: Early Treatment for Acute ACL Tear

• Sponsor: Cale Jacobs (Other)
• Overall Status: Completed
• CT.gov ID: NCT01692756
• Collaborator: Vanderbilt University (Other)
• Enrollment: 49
• Location: 1
• Arms: 4
• Duration (Months): 47.2
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

This research study is the first of its kind and will allow health care professionals and researchers to answer many questions about the reasons why anterior cruciate ligament (ACL) injury leads to knee pain and disability and osteoarthritis. We also hope that this study will be the beginning of new, more powerful and safer drugs to help patients with ACL injuries heal sooner and return to sports or daily activities pain free. Study participants will be recruited from the University of Kentucky and Vanderbilt University.

The purpose of this research is to gather information on how safe and effective Kenalog® is in alleviating knee pain following ACL rupture.

Condition or Disease	Intervention/Treatment	Phase
Anterior Cruciate Ligament (ACL) Tears	Drug: Kenalog or placebo; Drug: Kenalog then Placebo; Drug: Kenalog; Drug: Placebo	Phase 2

Detailed Description

Injury to the knee during sports participation often involves partial of full detachment of the ACL. ACL tears cause pain, swelling and inflammation. While the swelling and inflammation usually goes away in time, individuals with ACL injuries may experience pain and notice knee instability (knee slipping, etc.). Often surgery can repair or replace the ACL within the joint, allowing individuals the ability to walk or run again pain free or participate in sports. Unfortunately, osteoarthritis of the knee, which also causes pain and swelling, can occur in that same knee 10-20 years later for reasons which are not well understood.

In this research study, we hope to prevent and reduce the initial post-operative pain. The reduction of pain will allow for earlier movement of the knee joint and preparation for surgery. It may also reduce the risk to develop osteoarthritis in individuals with ACL injuries by treating them within 1-2 days after their injury.

Study Design

• Study Type: Interventional
• Actual Enrollment: 49 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Early Anti-inflammatory Treatment in Patients With Acute ACL Tear
• Study Start Date: Mar 1, 2013
• Actual Primary Completion Date: Feb 5, 2017
• Actual Study Completion Date: Feb 5, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Kenalog or Placebo Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later.	Drug: Kenalog or placebo; Other Names: Drug: Kenalog Other Names: triamcinolone acetonide injectable suspension Drug Placebo (for Kenalog) physiologic Saline solution
Experimental: Kenalog then placebo Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury.	Drug: Kenalog then Placebo; Other Names: Drug: Kenalog Other Names: triamcinolone acetonide injectable suspension Drug Placebo (for Kenalog) physiologic saline solution
Experimental: Kenalog only Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog®	Drug: Kenalog; Other Names: Drug: Kenalog Other Names: triamcinolone acetonide injectable suspension
Placebo Comparator: Placebo subjects will receive two consecutive intra-articular saline placebo injections at the same time periods.	Drug: Placebo; Other Names: Drug Placebo (for Kenalog) physiologic saline solution

Outcome Measures

Primary Outcome Measures

1. Participant Pain Assessment [Up to seven days]

   Participants with be given a Visual Analog Scale (VAS) pain assessment questionnaire which scores the participant's perceived pain on a scale of 0-10 were zero is no pain and 10 is the worst pain imaginable. The scale will be administered during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

Secondary Outcome Measures

1. Efficacy of Kenalog to Alleviate Knee Pain [Up to seven days]

   The efficacy of Kenalog with be determined using the Knee Injury and Osteoarthritis Outcome Score (KOOS) instrument. Participants will self-report knee pain and function through the KOOS questionnaire during the initial orthopedic consult and during the pre-op assessment prior to surgery, between 1 and 7 days later. The scale scores range from 100 (no symptoms) to zero (extreme symptoms).

2. Synovial Interleukin-1α (IL-1α) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1α concentration using an immunoassay. Data will be presented as the change in IL-1α concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

3. Synovial Interleukin-1β (IL-1β) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1β concentration using an immunoassay. Data will be presented as the change in IL-1β concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

4. Synovial Interleukin-1 Receptor Antagonist (IL-1ra) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1ra concentration using an immunoassay. Data will be presented as the change in IL-1ra concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

5. Synovial C-terminal Peptide II (CTXII) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure CTXII concentration using an immunoassay. Data will be presented as the change in CTXII concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

6. Synovial Cartilage Oligomeric Matrix Protein (COMP) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure COMP concentration using an immunoassay. Data will be presented as the change in COMP concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

7. Synovial Glycosaminoglycans (GAG) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure GAG concentration using an immunoassay. Data will be presented as the change in GAG concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

8. Synovial Type I Collagen Cross-Linked N-Telopeptide (NTX-I) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure NTX-I concentration using an immunoassay. Data will be presented as the change in NTX-I concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

9. Synovial TNF-stimulated Gene 6 Protein (TSG-6) Concentration [Up to seven days]

   Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure TSG-6 concentration using an immunoassay. Data will be presented as the change in TSG-6 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

10. Synovial Matrix Metalloproteinase 1 (MMP-1) Concentration [Up to seven days]

    Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-1 concentration using an immunoassay. Data will be presented as the change in MMP-1 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

11. Synovial Matrix Metalloproteinase 3 (MMP-3) Concentration [Up to seven days]

    Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-3 concentration using an immunoassay. Data will be presented as the change in MMP-3 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

12. Synovial Matrix Metalloproteinase 9 (MMP-9) Concentration [Up to seven days]

    Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-9 concentration using an immunoassay. Data will be presented as the change in MMP-9 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 14 Years to 33 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• currently participating in sporting activities

• Normal contralateral knee status

• Anterior Cruciate Ligament (ACL) injury occurred while playing a sporting activity

Exclusion Criteria:

• underlying inflammatory disease (i.e. Rheumatoid Arthritis, Psoriatic Arthritis, etc.)

• have been diagnosed with hepatitis B or tuberculosis

• currently have an infection, including infection of the skin

• have a disease that weakens your immune system such as diabetes, cancer, HIV or AIDs

• other major medical condition requiring treatment with immunosuppressant or modulating drugs.

• A history of chronic use of non-steroidal anti-inflammatory drugs

• previous exposure or allergic reaction to Kenalog

• prior knee surgery (Ipsilateral or contralateral)

• have received any investigational drug with 4 weeks of study Visit 1

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	UK HeathCare Sports Medicine	Lexington	Kentucky	United States	40517

Sponsors and Collaborators

• Cale Jacobs
• Vanderbilt University

Investigators

• Principal Investigator: Christian Lattermann, MD, University of Kentucky, Department of Orthopaedic Surgery

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 4, 2015

More Information

Publications

None provided.

• Responsible Party: Cale Jacobs, Sponsor/Investigator, University of Kentucky
• ClinicalTrials.gov Identifier: NCT01692756
• Other Study ID Numbers: 12-0706
• First Posted: Sep 25, 2012
• Last Update Posted: Dec 5, 2018
• Last Verified: Nov 1, 2018

• Additional relevant MeSH terms: Anterior Cruciate Ligament Injuries; Triamcinolone; Triamcinolone Acetonide; Triamcinolone hexacetonide; Pharmaceutical Solutions; Triamcinolone diacetate

Study Results

Participant Flow

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Period Title: Overall Study
STARTED	12	12	13	12
COMPLETED	11	11	11	12
NOT COMPLETED	1	1	2	0

Baseline Characteristics

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo	Total
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo	Total of all reporting groups
Overall Participants	11	11	11	12	45
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	18.45 (2.99)	19.60 (4.12)	24.06 (6.57)	17.80 (2.14)	19.9 (4.8)
Sex: Female, Male (Count of Participants)
Female	3 27.3%	4 36.4%	5 45.5%	7 58.3%	19 42.2%
Male	8 72.7%	7 63.6%	6 54.5%	5 41.7%	26 57.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%	0 0%
Black or African American	1 9.1%	0 0%	1 9.1%	4 33.3%	6 13.3%
White	10 90.9%	10 90.9%	10 90.9%	8 66.7%	38 84.4%
More than one race	0 0%	1 9.1%	0 0%	0 0%	1 2.2%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	11 100%	11 100%	11 100%	12 100%	45 100%
Knee Injury and Osteoarthritis Scale (KOOS) Pain Subscale (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	49.75 (19.10)	58.33 (15.42)	50.25 (24.61)	46.30 (25.02)	51.05 (21.2)

Outcome Measures

1. Primary Outcome

Title	Participant Pain Assessment
Description	Participants with be given a Visual Analog Scale (VAS) pain assessment questionnaire which scores the participant's perceived pain on a scale of 0-10 were zero is no pain and 10 is the worst pain imaginable. The scale will be administered during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

A total of 4 patients (Group 1 n:1, Group 2 n:1, Group 4 n:2) overlooked completing the VAS. This was not realized until the patients had left the study visit preventing the investigator from collecting the information.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	11	10
Mean (Standard Deviation) [units on a scale]	-3.9 (2.8)	-2.2 (2.2)	-3.6 (3.0)	-4.3 (3.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.33
	Comments
	Method	Kruskal-Wallis
	Comments

2. Secondary Outcome

Title	Efficacy of Kenalog to Alleviate Knee Pain
Description	The efficacy of Kenalog with be determined using the Knee Injury and Osteoarthritis Outcome Score (KOOS) instrument. Participants will self-report knee pain and function through the KOOS questionnaire during the initial orthopedic consult and during the pre-op assessment prior to surgery, between 1 and 7 days later. The scale scores range from 100 (no symptoms) to zero (extreme symptoms).
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	11	11	11	12
Mean (Standard Deviation) [units on a scale]	37.37 (17.50)	18.94 (11.02)	30.56 (23.17)	28.93 (22.36)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.08
	Comments
	Method	Kruskal-Wallis
	Comments

3. Secondary Outcome

Title	Synovial Interleukin-1α (IL-1α) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1α concentration using an immunoassay. Data will be presented as the change in IL-1α concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

The values for 3 patients (Gp1 n:1, Gp 2 n:1, Gp 3 n:1) were below the limits of detection and were not included in the analysis.Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined 1 aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	9	9	9	12
Mean (Standard Deviation) [pg/mL]	4.30 (6.59)	7.68 (13.15)	1.77 (4.43)	3.11 (5.03)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.93
	Comments
	Method	Kruskal-Wallis
	Comments

4. Secondary Outcome

Title	Synovial Interleukin-1β (IL-1β) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1β concentration using an immunoassay. Data will be presented as the change in IL-1β concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

The values for two patients (Gp1 n:1, Gp 2 n:1) were below the limits of detection and were not included in the analysis. Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined 1 aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	9	9	10	12
Mean (Standard Deviation) [pg/mL]	-1.08 (2.87)	0.75 (1.98)	-0.28 (0.37)	-0.19 (0.29)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.13
	Comments
	Method	Kruskal-Wallis
	Comments

5. Secondary Outcome

Title	Synovial Interleukin-1 Receptor Antagonist (IL-1ra) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure IL-1ra concentration using an immunoassay. Data will be presented as the change in IL-1ra concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [pg/mL]	-3352.5 (8285.5)	-4955.6 (12,939.6)	-7278.4 (12,581.9)	-6888.5 (8364.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.15
	Comments
	Method	Kruskal-Wallis
	Comments

6. Secondary Outcome

Title	Synovial C-terminal Peptide II (CTXII) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure CTXII concentration using an immunoassay. Data will be presented as the change in CTXII concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Group 1 n:1, Group 2 n:1) and 1 patient declined the pre-op assessment aspiration (Group 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [ng/mL]	0.32 (0.21)	0.23 (0.27)	0.19 (0.34)	1.32 (1.10)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.003
	Comments
	Method	Kruskal-Wallis
	Comments

7. Secondary Outcome

Title	Synovial Cartilage Oligomeric Matrix Protein (COMP) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure COMP concentration using an immunoassay. Data will be presented as the change in COMP concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Group 1 n:1, Group 2 n:1) and 1 patient declined the pre-op assessment aspiration (Group 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [μg/mL]	-4.9 (17.5)	-21.7 (24.1)	-11.7 (7.1)	-22.1 (5.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.007
	Comments
	Method	Kruskal-Wallis
	Comments

8. Secondary Outcome

Title	Synovial Glycosaminoglycans (GAG) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure GAG concentration using an immunoassay. Data will be presented as the change in GAG concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [μg/mL]	-73.1 (176.7)	155.8 (132.4)	-49.0 (252.5)	-167.4 (140.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.63
	Comments
	Method	Kruskal-Wallis
	Comments

9. Secondary Outcome

Title	Synovial Type I Collagen Cross-Linked N-Telopeptide (NTX-I) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure NTX-I concentration using an immunoassay. Data will be presented as the change in NTX-I concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [µg/mL]	3.5 (7.7)	0.6 (4.0)	2.6 (3.6)	5.8 (6.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.17
	Comments
	Method	Kruskal-Wallis
	Comments

10. Secondary Outcome

Title	Synovial TNF-stimulated Gene 6 Protein (TSG-6) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure TSG-6 concentration using an immunoassay. Data will be presented as the change in TSG-6 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [ng/ml]	68.0 (266.0)	57.6 (244.5)	111.4 (180.5)	-4.9 (224.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.62
	Comments
	Method	Kruskal-Wallis
	Comments

11. Secondary Outcome

Title	Synovial Matrix Metalloproteinase 1 (MMP-1) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-1 concentration using an immunoassay. Data will be presented as the change in MMP-1 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [ng/mL]	249.0 (745.9)	-183.0 (245.5)	-395.5 (472.2)	-100.4 (557.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.02
	Comments
	Method	Kruskal-Wallis
	Comments

12. Secondary Outcome

Title	Synovial Matrix Metalloproteinase 3 (MMP-3) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-3 concentration using an immunoassay. Data will be presented as the change in MMP-3 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [ng/mL]	2702.9 (3937.2)	504.0 (1705.9)	-512.4 (2175.0)	1295.9 (2414.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.20
	Comments
	Method	Kruskal-Wallis
	Comments

13. Secondary Outcome

Title	Synovial Matrix Metalloproteinase 9 (MMP-9) Concentration
Description	Participants will have a knee joint aspiration during their initial orthopedic consult and during pre-op assessment. Synovial fluid will be aspirated and spun at 3500RPM for 10 minutes then the supernatant will be pipetted and frozen. The supernatant will be used to measure MMP-9 concentration using an immunoassay. Data will be presented as the change in MMP-9 concentration from knee aspirate collected during the initial orthopedic consult after injury and during the participant's pre-operative assessment, usually 1-7 days after the initial consult.
Time Frame	Up to seven days

Outcome Measure Data

Analysis Population Description

Two other patients had dry knee aspirations, where the aspiration was performed but no fluid was collected, (Gp 1 n:1, Gp 2 n:1) and 1 patient declined the pre-op assessment aspiration (Gp 3 n:1) preventing analysis on these patients.

Arm/Group Title	Kenalog or Placebo	Kenalog Then Placebo	Kenalog Only	Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo	Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
Measure Participants	10	10	10	12
Mean (Standard Deviation) [ng/mL]	-71.1 (15.9)	-28.9 (42.6)	-17.7 (18.8)	-14.0 (24.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Kenalog or Placebo, Kenalog Then Placebo, Kenalog Only, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.87
	Comments
	Method	Kruskal-Wallis
	Comments

Adverse Events

Time Frame	Over the course of 12months.
Adverse Event Reporting Description	Patients were approached and asked about any adverse events at regular study and/or clinic visits.
Arm/Group Title	Kenalog or Placebo		Kenalog Then Placebo		Kenalog Only		Placebo
Arm/Group Description	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later. Kenalog or placebo		Subjects will initially receive 40mg injection of Kenalog® 1-2 days after injury and saline placebo at 12-14 days post injury. Kenalog then Placebo		Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog® Kenalog		subjects will receive two consecutive intra-articular saline placebo injections at the same time periods. Placebo
All Cause Mortality
	Kenalog or Placebo		Kenalog Then Placebo		Kenalog Only		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)
Serious Adverse Events
	Kenalog or Placebo		Kenalog Then Placebo		Kenalog Only		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/11 (0%)		0/11 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	Kenalog or Placebo		Kenalog Then Placebo		Kenalog Only		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/11 (63.6%)		4/11 (36.4%)		6/11 (54.5%)		5/12 (41.7%)
Gastrointestinal disorders
Nausea or Hives/Rash from post op pain meds	0/11 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	1/12 (8.3%)	1
General disorders
Knee Effusion Post-Op	1/11 (9.1%)	1	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Knee Effusion from Unanticipated Accident	1/11 (9.1%)	1	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Arthrofibrosis	1/11 (9.1%)	1	0/11 (0%)	0	2/11 (18.2%)	2	0/12 (0%)	0
Nosebleed	0/11 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Strep Throat	0/11 (0%)	0	0/11 (0%)	0	0/11 (0%)	0	1/12 (8.3%)	1
Persistent Low Leg Pain	0/11 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Stitch Abscess	0/11 (0%)	0	1/11 (9.1%)	1	0/11 (0%)	0	0/12 (0%)	0
Musculoskeletal and connective tissue disorders
ACL Re-Tear	4/11 (36.4%)	4	1/11 (9.1%)	1	0/11 (0%)	0	1/12 (8.3%)	1
Cervical Strain after Motor Vehicle Accident	0/11 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0
Infrapatella scarring/pain	0/11 (0%)	0	0/11 (0%)	0	1/11 (9.1%)	1	0/12 (0%)	0

Limitations/Caveats

[Not Specified]

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.