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
  Purpose

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.


Condition Intervention Phase
Knee Injury
Drug: Anakinra
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: IL-1ra for Prevention of Chondropathy Following Knee Injury

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • pain [ Time Frame: 4 and 30 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • chondropathy score [ Time Frame: 30-60 days ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: March 2006
Study Completion Date: June 2007
Primary Completion Date: June 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Intra-articular IL-1Ra
Drug: Anakinra
150 mg IL1Ra ia x1 vs saline ia x1
Other Name: Kineret
Placebo Comparator: 2
Intra-articular saline
Drug: Anakinra
150 mg IL1Ra ia x1 vs saline ia x1
Other Name: Kineret

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.

  Eligibility

Ages Eligible for Study:   18 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00332254

Locations
United States, North Carolina
Duke University Sports Medicine Clinic
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Duke University
Investigators
Study Chair: Virginia B Kraus, MD, PhD Duke University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Duke University
ClinicalTrials.gov Identifier: NCT00332254     History of Changes
Other Study ID Numbers: Pro00014439, 7939-05-11
Study First Received: May 30, 2006
Last Updated: May 29, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Anterior cruciate ligament tear
Meniscus tear
Chondral injury

Additional relevant MeSH terms:
Knee Injuries
Wounds and Injuries
Leg Injuries
Interleukin 1 Receptor Antagonist Protein
Antirheumatic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 20, 2014