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

Tracking Information

• First Submitted Date: September 11, 2012
• First Posted Date: September 25, 2012
• Results First Submitted Date: April 2, 2018
• Results First Posted Date: November 13, 2018
• Last Update Posted Date: December 5, 2018
• Study Start Date: March 2013
• Actual Primary Completion Date: February 5, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 13, 2018)

Participant Pain Assessment [ Time Frame: 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.

Original Primary Outcome Measures (submitted: September 24, 2012)

Efficacy of IL-1Ra to alleviate knee pain [ Time Frame: Patients will be evaluated for changes in pain at 5 post-injury time points (1-2 days), 12-14 days, 2 weeks post-op, 4 weeks post-op and 6 months post-op) ]

This trial will use the standardized patient self-report Knee Injury and Osteoarthritis Outcome Score (KOOS) instrument to assess pain and function in response to the intervention for acute ACL injury. This trial will supplement the KOOS with function score assessments from the International Knee Documentation Committee (IKDC) form for evaluation of knee ligament injuries

Current Secondary Outcome Measures (submitted: October 13, 2018)

• Efficacy of Kenalog to Alleviate Knee Pain [ Time Frame: 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-1α (IL-1α) Concentration [ Time Frame: 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 Interleukin-1β (IL-1β) Concentration [ Time Frame: 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 Interleukin-1 Receptor Antagonist (IL-1ra) Concentration [ Time Frame: 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 C-terminal Peptide II (CTXII) Concentration [ Time Frame: 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 Cartilage Oligomeric Matrix Protein (COMP) Concentration [ Time Frame: 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 Glycosaminoglycans (GAG) Concentration [ Time Frame: 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 [ Time Frame: 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 TNF-stimulated Gene 6 Protein (TSG-6) Concentration [ Time Frame: 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 1 (MMP-1) Concentration [ Time Frame: 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 Matrix Metalloproteinase 3 (MMP-3) Concentration [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: September 24, 2012)

IL-1Ra therapy improves levels of a panel of inflammatory (cytokine), meniscus and cartilage metabolism and oxidative stress biomarkers [ Time Frame: 1-7 days, 10-17 days after injury and at time of surgery ]

Biomarkers to be tested include IL-1α, IL-1β, Collagen type I (NtxI) and collagen type II (CTXII) breakdown products, cartilage oligomeric protein (COMP) and glycomsaminoglycan (GAG) and Xanthine Oxidase. Additionally, the change in IL-1α/β levels in the IL-1Ra treated and placebo individuals will be evaluated specifically for association with pain and function outcomes.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Early Treatment for Acute ACL Tear
• Official Title: Early Anti-inflammatory Treatment in Patients With Acute ACL Tear

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.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Anterior Cruciate Ligament (ACL) Tears

Intervention

• Drug: Kenalog or placebo
  Other Names:

  • Drug: Kenalog
  • Other Names:
  • triamcinolone acetonide injectable suspension
  • Drug Placebo (for Kenalog)
  • physiologic Saline solution
• Drug: Kenalog then Placebo
  Other Names:

  • Drug: Kenalog
  • Other Names:
  • triamcinolone acetonide injectable suspension
  • Drug Placebo (for Kenalog)
  • physiologic saline solution
• Drug: Kenalog
  Other Names:

  • Drug: Kenalog
  • Other Names:
  • triamcinolone acetonide injectable suspension
• Drug: Placebo
  Other Names:

  • Drug Placebo (for Kenalog)
  • physiologic saline solution

Study Arms

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

Publications *

• 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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 13, 2018): 49
• Original Estimated Enrollment (submitted: September 24, 2012): 68
• Actual Study Completion Date: February 5, 2017
• Actual Primary Completion Date: February 5, 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 14 Years to 33 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01692756
• Other Study ID Numbers: 12-0706
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Cale Jacobs, University of Kentucky
• Original Responsible Party: Christian Lattermann, University of Kentucky, Sponsor/Investigator
• Current Study Sponsor: Cale Jacobs
• Original Study Sponsor: Christian Lattermann
• Collaborators: Vanderbilt University

Investigators

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

• PRS Account: University of Kentucky
• Verification Date: November 2018