Early Treatment for Acute ACL Tear (AAA)

• ClinicalTrials.gov Identifier: NCT01692756
• Recruitment Status: Completed
• First Posted: September 25, 2012
• Results First Posted: November 13, 2018
• Last Update Posted: December 5, 2018
• Sponsor: Cale Jacobs
• Collaborator: Vanderbilt University
• Information provided by (Responsible Party): Cale Jacobs, University of Kentucky

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Anterior Cruciate Ligament (ACL) Tears
• Interventions: Drug: Kenalog or placebo; Drug: Kenalog then Placebo; Drug: Kenalog; Drug: Placebo
• Enrollment: 49

Participant Flow

Recruitment Details
Pre-assignment Details

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 Number of Baseline Participants		11	11	11	12	45
Baseline Analysis Population Description		One patient was lost to follow-up (Group 1). Two patients withdrew prior to receiving treatment (Group 2, Group 3). One patient did not attend first study visit and did not receive allocated intervention (Group 3).
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	11 participants	11 participants	11 participants	12 participants	45 participants
		18.45 (2.99)	19.60 (4.12)	24.06 (6.57)	17.80 (2.14)	19.9 (4.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	11 participants	11 participants	12 participants	45 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); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	11 participants	11 participants	11 participants	12 participants	45 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
	Asian	0 0.0%	0 0.0%	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 0.0%	0 0.0%
	Black or African American	1 9.1%	0 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 0.0%	1 9.1%	0 0.0%	0 0.0%	1 2.2%
	Unknown or Not Reported	0 0.0%	0 0.0%	0 0.0%	0 0.0%	0 0.0%
Region of Enrollment; Measure Type: Count of Participants; Unit of measure: Participants
United States	Number Analyzed	11 participants	11 participants	11 participants	12 participants	45 participants
		11 100.0%	11 100.0%	11 100.0%	12 100.0%	45 100.0%
Knee Injury and Osteoarthritis Scale (KOOS) Pain Subscale [1]; Mean (Standard Deviation); Unit of measure: Units on a scale
	Number Analyzed	11 participants	11 participants	11 participants	12 participants	45 participants
		49.75 (19.10)	58.33 (15.42)	50.25 (24.61)	46.30 (25.02)	51.05 (21.2)
		[1] Measure Description: KOOS consists of 5 subscales with five questions per scale; Pain, other Symptoms, Function in daily living (ADL), Function in sport and recreation (Sport/Rec) and knee related Quality of life QOL. The last week is taken into consideration when answering the questions. Standardized answer options are given (5 Likert boxes) and each question gets a score from 0 to 4. A normalized score (100 indicating no symptoms and 0 indicating extreme symptoms) is calculated for each subscale. The baseline KOOS Pain scores are presented here.

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
Overall Number of Participants Analyzed	10	10	11	10
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.33
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	11	11	11	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.08
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	9	9	9	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.93
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	9	9	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.13
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.15
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.003
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.007
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.63
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.17
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.62
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.02
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.20
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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
Overall Number of Participants Analyzed	10	10	10	12
Mean (Standard Deviation); Unit of Measure: 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	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	.87
	Comments	[Not Specified]
	Method	Kruskal-Wallis
	Comments	[Not Specified]

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 (%)		Affected / at Risk (%)		Affected / at Risk (%)		Affected / at Risk (%)
Total	0/11 (0.00%)		0/11 (0.00%)		0/11 (0.00%)		0/12 (0.00%)
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 (0.00%)		0/11 (0.00%)		0/11 (0.00%)		0/12 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	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 (63.64%)		4/11 (36.36%)		6/11 (54.55%)		5/12 (41.67%)
Gastrointestinal disorders
Nausea or Hives/Rash from post op pain meds †	0/11 (0.00%)	0	0/11 (0.00%)	0	1/11 (9.09%)	1	1/12 (8.33%)	1
General disorders
Knee Effusion Post-Op †	1/11 (9.09%)	1	1/11 (9.09%)	1	0/11 (0.00%)	0	1/12 (8.33%)	1
Knee Effusion from Unanticipated Accident †	1/11 (9.09%)	1	0/11 (0.00%)	0	1/11 (9.09%)	1	0/12 (0.00%)	0
Arthrofibrosis †	1/11 (9.09%)	1	0/11 (0.00%)	0	2/11 (18.18%)	2	0/12 (0.00%)	0
Nosebleed †	0/11 (0.00%)	0	0/11 (0.00%)	0	0/11 (0.00%)	0	1/12 (8.33%)	1
Strep Throat †	0/11 (0.00%)	0	0/11 (0.00%)	0	0/11 (0.00%)	0	1/12 (8.33%)	1
Persistent Low Leg Pain †	0/11 (0.00%)	0	1/11 (9.09%)	1	0/11 (0.00%)	0	0/12 (0.00%)	0
Stitch Abscess †	0/11 (0.00%)	0	1/11 (9.09%)	1	0/11 (0.00%)	0	0/12 (0.00%)	0
Musculoskeletal and connective tissue disorders
ACL Re-Tear † [1]	4/11 (36.36%)	4	1/11 (9.09%)	1	0/11 (0.00%)	0	1/12 (8.33%)	1
Cervical Strain after Motor Vehicle Accident †	0/11 (0.00%)	0	0/11 (0.00%)	0	1/11 (9.09%)	1	0/12 (0.00%)	0
Infrapatella scarring/pain †	0/11 (0.00%)	0	0/11 (0.00%)	0	1/11 (9.09%)	1	0/12 (0.00%)	0
† Indicates events were collected by systematic assessment; [1] Re-Tear of the anterior cruciate ligament

Limitations and 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.

Results Point of Contact

• Name/Title: Cale Jacobs, ATC, PhD
• Organization: Univerisity of Kentucky
• Phone: 8592183065
• EMail: Kycartilagedoc@gmail.com

Publications of Results:

Lattermann C, Jacobs CA, Proffitt Bunnell M, Huston LJ, Gammon LG, Johnson DL, Reinke EK, Huebner JL, Kraus VB, Spindler KP. A Multicenter Study of Early Anti-inflammatory Treatment in Patients With Acute Anterior Cruciate Ligament Tear. Am J Sports Med. 2017 Feb;45(2):325-333. doi: 10.1177/0363546516666818. Epub 2016 Oct 7.

Lattermann C, Jacobs CA, Bunnell MP, Jochimsen KN, Abt JP, Reinke EK, Gammon LG, Huebner JL, Kraus VB, Spindler KP. Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis. J Orthop Res. 2017 Mar;35(3):641-650. doi: 10.1002/jor.23329. Epub 2016 Jun 30.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

King JD, Rowland G, Villasante Tezanos AG, Warwick J, Kraus VB, Lattermann C, Jacobs CA. Joint Fluid Proteome after Anterior Cruciate Ligament Rupture Reflects an Acute Posttraumatic Inflammatory and Chondrodegenerative State. Cartilage. 2020 Jul;11(3):329-337. doi: 10.1177/1947603518790009. Epub 2018 Jul 22.

• Responsible Party: Cale Jacobs, University of Kentucky
• ClinicalTrials.gov Identifier: NCT01692756
• Other Study ID Numbers: 12-0706
• First Submitted: September 11, 2012
• First Posted: September 25, 2012
• Results First Submitted: April 2, 2018
• Results First Posted: November 13, 2018
• Last Update Posted: December 5, 2018