Study to Prevent Cartilage Damage Following Acute Knee Injury.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Duke University
ClinicalTrials.gov Identifier:
NCT00332254
First received: May 30, 2006
Last updated: May 29, 2013
Last verified: January 2008

May 30, 2006
May 29, 2013
March 2006
June 2007   (final data collection date for primary outcome measure)
pain [ Time Frame: 4 and 30 days ] [ Designated as safety issue: No ]
Evaluate symptomatic and biological response to intraarticularly administered IL-1ra within first month following acute joint injury,using established outcome measures
Complete list of historical versions of study NCT00332254 on ClinicalTrials.gov Archive Site
chondropathy score [ Time Frame: 30-60 days ] [ Designated as safety issue: No ]
Assess change in metabolic state of joint using cytokine profiles and cartilage biomarkers and intra-operative assessment of chondropathy will be performed.
Not Provided
Not Provided
 
Study to Prevent Cartilage Damage Following Acute Knee Injury.
IL-1ra for Prevention of Chondropathy Following Knee Injury

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Knee Injury
Drug: Anakinra
150 mg IL1Ra ia x1 vs saline ia x1
Other Name: Kineret
  • Experimental: 1
    Intra-articular IL-1Ra
    Intervention: Drug: Anakinra
  • Placebo Comparator: 2
    Intra-articular saline
    Intervention: Drug: Anakinra

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
June 2007
June 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Onset of injury less than 4 weeks prior to evaluation
  • Severe knee injury that requires surgery, including anterior cruciate ligament tear, meniscus tear and chondral injury
  • BMI less than 30
  • Age 18-30
  • Women will have serum pregnancy testing (bHCG) at time of entry and on follow-up evaluation and must agree to use an approved form of contraception during the study period.

Exclusion Criteria:

  • Prior signal joint injury requiring medical evaluation
  • History of arthritis or rheumatic disease
  • History of intra-articular corticosteroid in index joint
  • Septic joint
  • Evidence of chronic joint disease by plain radiograph
  • Fracture or multiple ligament tear
  • Pregnancy or lactation
  • Inability to give informed consent
Both
18 Years to 30 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00332254
Pro00014439, 7939-05-11
Yes
Duke University
Duke University
Not Provided
Study Chair: Virginia B Kraus, MD, PhD Duke University
Duke University
January 2008

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP