Study to Prevent Cartilage Damage Following Acute Knee Injury.
Condition: Knee Injury
MeSH terms: Wounds and Injuries; Knee Injuries
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Individuals who have had a severe knee injury have an increased risk of developing arthritis
      of the knee and at a much earlier age than would otherwise be expected. The swelling and
      inflammation that occur after injury are believed to be responsible for this cartilage
      damage. The cartilage (material that provides a cushion in the knee) is the primary
      protection from what is called degenerative arthritis or osteoarthritis. We hope to reduce
      this swelling and prevent the damage to cartilage that occurs after injury by injecting a
      medication that blocks one of the proteins responsible for inflammation and cartilage
      breakdown. This protein is called interleukin-1 and can be inhibited by an interleukin-1
      receptor antagonist called anakinra. Anakinra will be injected directly into the injured knee
      and response to the injection will be measured by symptoms and analysis of cartilage
      breakdown in the knee fluid and blood.
    

Detailed description: 
      Osteoarthritis is highly prevalent with significant impact on health care utilization and
      personal suffering. Injury predisposes to OA even after surgical correction (1, 2).
      Definitive therapy for established OA is lacking and current treatments are increasingly
      questioned with regard to long-term safety. Interleukin-1 is instrumental in OA pathogenesis
      (3-5). Recent studies by Chevalier demonstrated that intra-articular use of IL-1ra was safe
      in patients with established OA (6). We hope to show that IL-1ra will provide symptomatic
      benefit after knee injury as well as decreasing cartilage breakdown.

      The trial will consist of trial administering 150mg of Anakinra, or placebo, within 30 days
      of an acute knee injury that requires surgical repair. We hypothesize that higher IL-1 in
      synovial fluid after injury will predict greater symptomatic response to IL-1ra. Outcome
      measures will be functional and pain assessments at regular intervals before and after
      surgery (7, 8). Cartilage catabolism will be assessed with two primary measures. First we
      will assess degree of chondropathy via direct cartilage visualization and scoring at the time
      of arthroscopic repair (9). Secondly, the impact of IL-1ra on the inflammatory milieu will be
      determined through analysis of serum and synovial fluid cytokine levels and cartilage
      biomarkers at enrollment and again at the time of surgical repair.

      The impetus for this study is based on previous work done in animal models of OA, showing
      prevention of cartilage damage following surgically induced ACL injury (10-12). We believe
      that intra-articular delivery of anakinra within a short time following knee injury will
      improve patient function and pain reporting and will also prevent chondropathy that results
      from injury.
    

Intervention name(s): Anakinra
Intervention type(s): Drug
Intervention description(s): 150 mg IL1Ra ia x1 vs saline ia x1
Other intervention name(s): Kineret
Intervention MeSH terms: Interleukin 1 Receptor Antagonist Protein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Anterior cruciate ligament tear; Meniscus tear; Chondral injury