Early Treatment for Acute ACL Tear

Phase 2

Completed

Conditions: Anterior Cruciate Ligament (ACL) Tears

Interventions: Drug: Kenalog or placebo
Drug: Kenalog then Placebo
Drug: Placebo
Drug: Kenalog

Registration Number: NCT01692756

Lead Sponsor: Cale Jacobs

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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 49

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Kenalog or Placebo	Kenalog or placebo	Kenalog® (40mg) or saline placebo injection 1-2 days after ACL injury and 12-14 days later.
Kenalog then placebo	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.
Placebo	Placebo	subjects will receive two consecutive intra-articular saline placebo injections at the same time periods.
Kenalog only	Kenalog	Subjects will receive two consecutive (40 mg) intra-articular injections of Kenalog®

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.