Study to Prevent Cartilage Damage Following Acute Knee Injury.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT00332254

Recruitment Status : Completed

First Posted : June 1, 2006

Last Update Posted : May 30, 2013

Sponsor:

Information provided by (Responsible Party):

Duke University

Study Description

Brief 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.

Condition or disease	Intervention/treatment	Phase
Knee Injury	Drug: Anakinra	Phase 1 Phase 2

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.

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	IL-1ra for Prevention of Chondropathy Following Knee Injury
Study Start Date :	March 2006
Actual Primary Completion Date :	June 2007
Actual Study Completion Date :	June 2007

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Knee Injuries and Disorders

Drug Information available for: Anakinra

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
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

Outcome Measures

Primary Outcome Measures :

pain [ Time Frame: 4 and 30 days ]

Secondary Outcome Measures :

chondropathy score [ Time Frame: 30-60 days ]

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years to 30 Years (Adult)
Sexes Eligible for Study:	All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00332254

Locations

Layout table for location information

United States, North Carolina
Duke University Sports Medicine Clinic
Durham, North Carolina, United States, 27710

Sponsors and Collaborators

Duke University

Investigators

Layout table for investigator information

Study Chair:	Virginia B Kraus, MD, PhD	Duke University

More Information

Publications:

Gelber AC, Hochberg MC, Mead LA, Wang NY, Wigley FM, Klag MJ. Joint injury in young adults and risk for subsequent knee and hip osteoarthritis. Ann Intern Med. 2000 Sep 5;133(5):321-8.

Roos EM. Joint injury causes knee osteoarthritis in young adults. Curr Opin Rheumatol. 2005 Mar;17(2):195-200. Review.

Pelletier JP, DiBattista JA, Roughley P, McCollum R, Martel-Pelletier J. Cytokines and inflammation in cartilage degradation. Rheum Dis Clin North Am. 1993 Aug;19(3):545-68. Review.

Pelletier JP, McCollum R, Cloutier JM, Martel-Pelletier J. Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. J Rheumatol Suppl. 1995 Feb;43:109-14.

Lotz M. Cytokines in cartilage injury and repair. Clin Orthop Relat Res. 2001 Oct;(391 Suppl):S108-15. Review.

Chevalier X, Giraudeau B, Conrozier T, Marliere J, Kiefer P, Goupille P. Safety study of intraarticular injection of interleukin 1 receptor antagonist in patients with painful knee osteoarthritis: a multicenter study. J Rheumatol. 2005 Jul;32(7):1317-23.

Paxton EW, Fithian DC, Stone ML, Silva P. The reliability and validity of knee-specific and general health instruments in assessing acute patellar dislocation outcomes. Am J Sports Med. 2003 Jul-Aug;31(4):487-92.

Irrgang JJ, Anderson AF. Development and validation of health-related quality of life measures for the knee. Clin Orthop Relat Res. 2002 Sep;(402):95-109. Review.

Ayral X, Dougados M, Listrat V, Bonvarlet JP, Simonnet J, Poiraudeau S, Amor B. Chondroscopy: a new method for scoring chondropathy. Semin Arthritis Rheum. 1993 Apr;22(5):289-97.

Pelletier JP, Caron JP, Evans C, Robbins PD, Georgescu HI, Jovanovic D, Fernandes JC, Martel-Pelletier J. In vivo suppression of early experimental osteoarthritis by interleukin-1 receptor antagonist using gene therapy. Arthritis Rheum. 1997 Jun;40(6):1012-9.

Fernandes J, Tardif G, Martel-Pelletier J, Lascau-Coman V, Dupuis M, Moldovan F, Sheppard M, Krishnan BR, Pelletier JP. In vivo transfer of interleukin-1 receptor antagonist gene in osteoarthritic rabbit knee joints: prevention of osteoarthritis progression. Am J Pathol. 1999 Apr;154(4):1159-69.

Caron JP, Fernandes JC, Martel-Pelletier J, Tardif G, Mineau F, Geng C, Pelletier JP. Chondroprotective effect of intraarticular injections of interleukin-1 receptor antagonist in experimental osteoarthritis. Suppression of collagenase-1 expression. Arthritis Rheum. 1996 Sep;39(9):1535-44.

Roos EM, Roos HP, Lohmander LS, Ekdahl C, Beynnon BD. Knee Injury and Osteoarthritis Outcome Score (KOOS)--development of a self-administered outcome measure. J Orthop Sports Phys Ther. 1998 Aug;28(2):88-96.

Kessler S, Lang S, Puhl W, Stöve J. [The Knee Injury and Osteoarthritis Outcome Score--a multifunctional questionnaire to measure outcome in knee arthroplasty]. Z Orthop Ihre Grenzgeb. 2003 May-Jun;141(3):277-82. German.

Marks PH, Donaldson ML. Inflammatory cytokine profiles associated with chondral damage in the anterior cruciate ligament-deficient knee. Arthroscopy. 2005 Nov;21(11):1342-7.

Poole AR, Ionescu M, Fitzcharles MA, Billinghurst RC. The assessment of cartilage degradation in vivo: development of an immunoassay for the measurement in body fluids of type II collagen cleaved by collagenases. J Immunol Methods. 2004 Nov;294(1-2):145-53.

Matyas JR, Atley L, Ionescu M, Eyre DR, Poole AR. Analysis of cartilage biomarkers in the early phases of canine experimental osteoarthritis. Arthritis Rheum. 2004 Feb;50(2):543-52.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Kraus VB, Birmingham J, Stabler TV, Feng S, Taylor DC, Moorman CT 3rd, Garrett WE, Toth AP. Effects of intraarticular IL1-Ra for acute anterior cruciate ligament knee injury: a randomized controlled pilot trial (NCT00332254). Osteoarthritis Cartilage. 2012 Apr;20(4):271-8. doi: 10.1016/j.joca.2011.12.009. Epub 2012 Jan 10.

Catterall JB, Stabler TV, Flannery CR, Kraus VB. Changes in serum and synovial fluid biomarkers after acute injury (NCT00332254). Arthritis Res Ther. 2010;12(6):R229. doi: 10.1186/ar3216. Epub 2010 Dec 31.

Layout table for additonal information

Responsible Party:	Duke University
ClinicalTrials.gov Identifier:	NCT00332254
Other Study ID Numbers:	Pro00014439 7939-05-11 ( Other Identifier: Duke IRB# )
First Posted:	June 1, 2006 Key Record Dates
Last Update Posted:	May 30, 2013
Last Verified:	January 2008

Keywords provided by Duke University:


Anterior cruciate ligament tear Meniscus tear Chondral injury

Additional relevant MeSH terms:

Layout table for MeSH terms

Wounds and Injuries Knee Injuries Leg Injuries Interleukin 1 Receptor Antagonist Protein Antirheumatic Agents

To Top