Study to Prevent Cartilage Damage Following Acute Knee Injury.

NCT ID: NCT00332254

Last Updated: 2013-05-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2007-06-30

Brief Summary

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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

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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.

Conditions

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Knee Injury

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Intra-articular IL-1Ra

Group Type EXPERIMENTAL

Anakinra

Intervention Type DRUG

150 mg IL1Ra ia x1 vs saline ia x1

2

Intra-articular saline

Group Type PLACEBO_COMPARATOR

Anakinra

Intervention Type DRUG

150 mg IL1Ra ia x1 vs saline ia x1

Interventions

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Anakinra

150 mg IL1Ra ia x1 vs saline ia x1

Intervention Type DRUG

Other Intervention Names

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Kineret

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

30 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Duke University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Virginia B Kraus, MD, PhD

Role: STUDY_CHAIR

Duke University

Locations

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Duke University Sports Medicine Clinic

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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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. doi: 10.7326/0003-4819-133-5-200009050-00007.

Reference Type BACKGROUND
PMID: 10979876 (View on PubMed)

Roos EM. Joint injury causes knee osteoarthritis in young adults. Curr Opin Rheumatol. 2005 Mar;17(2):195-200. doi: 10.1097/01.bor.0000151406.64393.00.

Reference Type BACKGROUND
PMID: 15711235 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 8210574 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 7752112 (View on PubMed)

Lotz M. Cytokines in cartilage injury and repair. Clin Orthop Relat Res. 2001 Oct;(391 Suppl):S108-15. doi: 10.1097/00003086-200110001-00011.

Reference Type BACKGROUND
PMID: 11603695 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15996071 (View on PubMed)

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. doi: 10.1177/03635465030310040201.

Reference Type BACKGROUND
PMID: 12860533 (View on PubMed)

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. doi: 10.1097/00003086-200209000-00009.

Reference Type BACKGROUND
PMID: 12218475 (View on PubMed)

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. doi: 10.1016/s0049-0172(05)80008-3.

Reference Type BACKGROUND
PMID: 8511593 (View on PubMed)

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. doi: 10.1002/art.1780400604.

Reference Type BACKGROUND
PMID: 9182910 (View on PubMed)

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. doi: 10.1016/S0002-9440(10)65368-0.

Reference Type BACKGROUND
PMID: 10233854 (View on PubMed)

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. doi: 10.1002/art.1780390914.

Reference Type BACKGROUND
PMID: 8814066 (View on PubMed)

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. doi: 10.2519/jospt.1998.28.2.88.

Reference Type BACKGROUND
PMID: 9699158 (View on PubMed)

Kessler S, Lang S, Puhl W, Stove 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. doi: 10.1055/s-2003-40083. German.

Reference Type BACKGROUND
PMID: 12822074 (View on PubMed)

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. doi: 10.1016/j.arthro.2005.08.034.

Reference Type BACKGROUND
PMID: 16325085 (View on PubMed)

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. doi: 10.1016/j.jim.2004.09.005.

Reference Type BACKGROUND
PMID: 15637808 (View on PubMed)

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. doi: 10.1002/art.20027.

Reference Type BACKGROUND
PMID: 14872497 (View on PubMed)

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.

Reference Type DERIVED
PMID: 22273632 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21194441 (View on PubMed)

Other Identifiers

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7939-05-11

Identifier Type: OTHER

Identifier Source: secondary_id

Pro00014439

Identifier Type: -

Identifier Source: org_study_id

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