Clinical trial NCT00604539: Effect of Chondroitin Sulphate on Synovial Inflammation in Patients With Osteoarthritis of the Knee
Official title: Study of the Effect of Chondroitin Sulphate on Synovial Inflammation in Patients With Osteoarthritis of the Knee
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Synovitis
Osteoarthritis
Joint Diseases
Muskuloskeletal Diseases
Keywords: Chondroitin sulphate
Synovitis
Knee osteoarthritis
Magnetic Resonance Imaging
Lead sponsor: Bioiberica
Sponsor class: INDUSTRY
First posted: 2008-01-30
Enrollment: 70
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine the effect of a chondroitin sulphate conventional treatment on the degree of severity of synovitis, as measured by magnetic resonance in patients with knee OA with clinical synovitis.


Eligibility criteria: Inclusion Criteria:

* Primary OA of the knee according to ACR with synovitis criteria (warmth, swelling or effusion);
* OA of radiological stages 2 and 3 according to Kellgren-Lawrence;
* Minimum joint space width ≥2 mm in the medial femorotibial compartment on standing knee X-ray;
* VAS of pain while walking ≥40 mm.

Exclusion Criteria:

* Known allergy to chondroitin sulphate;
* Progressive or serious pathologies (cancer, AIDS,...);
* Other bone and articular diseases (antecedents and/or current signs) such as chondrocalcinosis, Paget's disease, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, hemochromatosis, Wilson's disease, osteochondromatosis;
* Corticosteroids (oral, injectable), indomethacin, therapeutic dose of glucosamine or chondroitin sulphate during the 12 weeks preceding inclusion;
* Hyaluronic Acid (intra-articular pathway) during the 26 weeks preceding inclusion;
* Radioactive synovectomy during the 12 weeks preceding inclusion;
* If the patient is receiving NSAID at baseline (D0), it should be maintained at a stable dosage as much as possible from D0 to D180. In the open phase of the study (D180 to D360), NSAID will also be allowed as rescue medication along with acetaminophen.

Primary outcomes:
measure: Evaluation of the change in the severity of synovitis measured by MRI according to the modified methods of Loeuille et al. after chondroitin sulphate treatment in patients with knee OA and clinical signs of synovitis
timeFrame: One year
Secondary outcomes:
measure: Changes of cartilage volume and subchondral bone lesions
timeFrame: One year
measure: Pain measured by VAS
timeFrame: One year
measure: WOMAC index
timeFrame: One year
measure: SF-36 Health Questionaire
timeFrame: One year
measure: Assessment of joint swelling, effusion
timeFrame: One year
measure: Use of rescue medication
timeFrame: One year
measure: Tolerability
timeFrame: One year
measure: Adverse events
timeFrame: One year
Other outcomes:
Locations:
city: Montréal
country: Canada
facility: Inst. De Rhumatologie
state: Quebec
city: Ste-Foy
country: Canada
facility: Groupe de recherche en rhumatologie et maladies osseuses
state: Quebec
city: Ste-Foy
country: Canada
facility: Centre de rhumatologie St-Louis
state: Quebec
city: Trois-Rivieres
country: Canada
facility: Centre de recherche musculo-squelettique
state: Quebec
Study officials:
affiliation: ArthroLab Inc.
name: Jean-Pierre Pelletier, Prof., Dr.
role: PRINCIPAL_INVESTIGATOR
affiliation: ArthroLab Inc.
name: Johanne Martel-Pelletier, Prof., Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Berthiaume MJ, Raynauld JP, Martel-Pelletier J, Labonte F, Beaudoin G, Bloch DA, Choquette D, Haraoui B, Altman RD, Hochberg M, Meyer JM, Cline GA, Pelletier JP. Meniscal tear and extrusion are strongly associated with progression of symptomatic knee osteoarthritis as assessed by quantitative magnetic resonance imaging. Ann Rheum Dis. 2005 Apr;64(4):556-63. doi: 10.1136/ard.2004.023796. Epub 2004 Sep 16.
citation: Fajardo M, Di Cesare PE. Disease-modifying therapies for osteoarthritis : current status. Drugs Aging. 2005;22(2):141-61. doi: 10.2165/00002512-200522020-00005.
citation: Clegg DO, Reda DJ, Harris CL, Klein MA, O'Dell JR, Hooper MM, Bradley JD, Bingham CO 3rd, Weisman MH, Jackson CG, Lane NE, Cush JJ, Moreland LW, Schumacher HR Jr, Oddis CV, Wolfe F, Molitor JA, Yocum DE, Schnitzer TJ, Furst DE, Sawitzke AD, Shi H, Brandt KD, Moskowitz RW, Williams HJ. Glucosamine, chondroitin sulfate, and the two in combination for painful knee osteoarthritis. N Engl J Med. 2006 Feb 23;354(8):795-808. doi: 10.1056/NEJMoa052771.
citation: Hochberg MC, Altman RD, Brandt KD, Clark BM, Dieppe PA, Griffin MR, Moskowitz RW, Schnitzer TJ. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. American College of Rheumatology. Arthritis Rheum. 1995 Nov;38(11):1541-6. doi: 10.1002/art.1780381104.
citation: Leeb BF, Schweitzer H, Montag K, Smolen JS. A metaanalysis of chondroitin sulfate in the treatment of osteoarthritis. J Rheumatol. 2000 Jan;27(1):205-11.
citation: Loeuille D, Chary-Valckenaere I, Champigneulle J, Rat AC, Toussaint F, Pinzano-Watrin A, Goebel JC, Mainard D, Blum A, Pourel J, Netter P, Gillet P. Macroscopic and microscopic features of synovial membrane inflammation in the osteoarthritic knee: correlating magnetic resonance imaging findings with disease severity. Arthritis Rheum. 2005 Nov;52(11):3492-501. doi: 10.1002/art.21373.
citation: McAlindon TE, LaValley MP, Gulin JP, Felson DT. Glucosamine and chondroitin for treatment of osteoarthritis: a systematic quality assessment and meta-analysis. JAMA. 2000 Mar 15;283(11):1469-75. doi: 10.1001/jama.283.11.1469.
citation: Michel BA, Stucki G, Frey D, De Vathaire F, Vignon E, Bruehlmann P, Uebelhart D. Chondroitins 4 and 6 sulfate in osteoarthritis of the knee: a randomized, controlled trial. Arthritis Rheum. 2005 Mar;52(3):779-86. doi: 10.1002/art.20867.
citation: Morreale P, Manopulo R, Galati M, Boccanera L, Saponati G, Bocchi L. Comparison of the antiinflammatory efficacy of chondroitin sulfate and diclofenac sodium in patients with knee osteoarthritis. J Rheumatol. 1996 Aug;23(8):1385-91.
citation: Zhang W, Doherty M, Arden N, Bannwarth B, Bijlsma J, Gunther KP, Hauselmann HJ, Herrero-Beaumont G, Jordan K, Kaklamanis P, Leeb B, Lequesne M, Lohmander S, Mazieres B, Martin-Mola E, Pavelka K, Pendleton A, Punzi L, Swoboda B, Varatojo R, Verbruggen G, Zimmermann-Gorska I, Dougados M; EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). EULAR evidence based recommendations for the management of hip osteoarthritis: report of a task force of the EULAR Standing Committee for International Clinical Studies Including Therapeutics (ESCISIT). Ann Rheum Dis. 2005 May;64(5):669-81. doi: 10.1136/ard.2004.028886. Epub 2004 Oct 7.
citation: Raynauld JP, Martel-Pelletier J, Berthiaume MJ, Beaudoin G, Choquette D, Haraoui B, Tannenbaum H, Meyer JM, Beary JF, Cline GA, Pelletier JP. Long term evaluation of disease progression through the quantitative magnetic resonance imaging of symptomatic knee osteoarthritis patients: correlation with clinical symptoms and radiographic changes. Arthritis Res Ther. 2006;8(1):R21. doi: 10.1186/ar1875. Epub 2005 Dec 30.
citation: Richy F, Bruyere O, Ethgen O, Cucherat M, Henrotin Y, Reginster JY. Structural and symptomatic efficacy of glucosamine and chondroitin in knee osteoarthritis: a comprehensive meta-analysis. Arch Intern Med. 2003 Jul 14;163(13):1514-22. doi: 10.1001/archinte.163.13.1514.
citation: Uebelhart D, Malaise M, Marcolongo R, de Vathaire F, Piperno M, Mailleux E, Fioravanti A, Matoso L, Vignon E. Intermittent treatment of knee osteoarthritis with oral chondroitin sulfate: a one-year, randomized, double-blind, multicenter study versus placebo. Osteoarthritis Cartilage. 2004 Apr;12(4):269-76. doi: 10.1016/j.joca.2004.01.004.
citation: Wildi LM, Raynauld JP, Martel-Pelletier J, Beaulieu A, Bessette L, Morin F, Abram F, Dorais M, Pelletier JP. Chondroitin sulphate reduces both cartilage volume loss and bone marrow lesions in knee osteoarthritis patients starting as early as 6 months after initiation of therapy: a randomised, double-blind, placebo-controlled pilot study using MRI. Ann Rheum Dis. 2011 Jun;70(6):982-9. doi: 10.1136/ard.2010.140848. Epub 2011 Mar 1.