Early Treatment for Acute ACL Tear

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Early Anti-inflammatory Treatment in Patients With Acute ACL Tear

Conditions
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Anterior Cruciate Ligament (ACL) Tears

Intervention / Treatment
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* Drug: Kenalog or placebo
* Drug: Kenalog then Placebo
* Drug: Kenalog
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 14 Years
Maximum Age: 33 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Participant Pain Assessment | 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. | Up to seven days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Kenalog to Alleviate Knee Pain | 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). | Up to seven days | 
| Synovial Interleukin-1α (IL-1α) Concentration | 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. | Up to seven days | 
| Synovial Interleukin-1β (IL-1β) Concentration | 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. | Up to seven days | 
| Synovial Interleukin-1 Receptor Antagonist (IL-1ra) Concentration | 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. | Up to seven days | 
| Synovial C-terminal Peptide II (CTXII) Concentration | 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. | Up to seven days | 
| Synovial Cartilage Oligomeric Matrix Protein (COMP) Concentration | 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. | Up to seven days | 
| Synovial Glycosaminoglycans (GAG) Concentration | 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. | Up to seven days | 
| Synovial Type I Collagen Cross-Linked N-Telopeptide (NTX-I) Concentration | 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. | Up to seven days | 
| Synovial TNF-stimulated Gene 6 Protein (TSG-6) Concentration | 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. | Up to seven days | 
| Synovial Matrix Metalloproteinase 1 (MMP-1) Concentration | 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. | Up to seven days | 
| Synovial Matrix Metalloproteinase 3 (MMP-3) Concentration | 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. | Up to seven days | 
| Synovial Matrix Metalloproteinase 9 (MMP-9) Concentration | 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. | Up to seven days |