Clinical trial NCT01354145: Study of the Effect of Chondroitin Sulfate on Structural Changes in Knee Osteoarthritis Patients Assessed by MRI
Official title: Twenty-four Month Exploratory Study of the Effect of Chondroitin Sulphate on Structural Changes in Knee Osteoarthritis Patients as Assessed by MRI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Knee Osteoarthritis
Lead sponsor: Bioiberica
Sponsor class: INDUSTRY
First posted: 2011-05-16
Enrollment: 194
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 main purpose of this study is to compare the cartilage volume loss at the Baseline visit and after 24 months of treatment in patients treated with CHONDROITIN SULPHATE (CONDROSAN) 1200 mg daily vs. patients treated with CELECOXIB 200 mg daily.

Detailed description: To compare long term disease modifiying and symptomatic effects at the Baseline visit and after 24 months of treatment in patients treated with CHONDROITIN SULPHATE 1200 mg daily vs. patients treated with CELECOXIB 200 mg daily.

Eligibility criteria: Inclusion Criteria:

* Individuals of either sex, aged 40 years and more
* Subjects presenting primary OA of the knee according to ACR criteria with signs of synovitis (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, hypersensitivity to CELECOXIB, demonstrated allergic-type reactions to sulphonamides, experienced asthma, urticaria or allergic-type reactions after taking sulphonamides, aspirin (acetyl salicylic acid \[ASA\]), lactose or NSAIDs
* Active malignancy of any type or history of a malignancy within the last five years other than basal cell carcinoma
* Increased risk for prostate cancer, with prostate cancer, or with a history of prostate cancer within the last five years
* Subjects with other bone and articular diseases (antecedents and/or current signs) such as chondrocalcinosis, Paget's disease of the ipsilateral limb to the target knee, rheumatoid arthritis, aseptic osteonecrosis, gout, septic arthritis, ochronosis, acromegaly, haemochromatosis, Wilson's disease, osteochondromatosis seronegative spondylo-arthropathy, mixed connective tissue disease, collagen vascular disease, psoriasis, inflammatory bowel disease
* Isolated knee lateral compartment OA defined by joint space loss in the lateral compartment only
* Class IV functional capacity using the American Rheumatism Association criteria
* Have had surgery in any lower limb or arthroscopy, aspiration or lavage in any lower limb joint within 180 days of the Baseline Visit
* History of heart attack or stroke, or experienced serious chest pain related to heart disease, or who have had serious diseases of the heart such as congestive heart failure
* High risk of CV events, according to the AHA assessment of CV risk tables
* History of recurrent UGI ulceration or active inflammatory bowel disease (e.g., Crohn's disease or ulcerative colitis), a significant coagulation defect, or any other condition, which in the investigator's opinion might preclude the chronic use of CELECOXIB. Subjects may, at the Investigator's discretion, take a PPI or antacids daily as required
* Have been diagnosed as having or have been treated for oesophageal, gastric, pyloric channel, or duodenal ulceration within 30 days prior to receiving the first dose of study medication
* Subjects using corticosteroids (oral, injectable; exception of intraarticular/soft tissue injection at the exclusion of the target knee), indomethacin, tramadol, codeine, empracet, therapeutic dose of glucosamine or CHONDROITIN SULPHATE during the 12 weeks preceding inclusion
* Using hyaluronic acid (intra-articular target knee) during the 26 weeks preceding inclusion
* Using Natural Health Products (e.g. capsaicin, boswellia, willow bark), and creams and analgesic gels (e.g. camphor and alcohol based gels) during one week preceding baseline;
* Using Natural Health Products susceptible to increase the risk of bleeding (e.g. garlic, dong quai, etc.) during one week preceding baseline;
* Receiving radioactive synovectomy (target knee) during the 12 weeks preceding inclusion;
* Subjects who are receiving NSAID and do not want to stop during the study
* If treatment of osteoporosis (biphosphonates, SERMS, THS) is necessary, it will have to be continued, unmodified, for the entire duration of the study
* Have used medications with MMP-inhibitory properties (e.g. tetracycline or structurally related compounds) within 28 days prior to the Baseline Visit
* Are taking lithium carbonate, phenytoin or anticoagulants (with the exception of ASA up to a maximum daily dose of 325 mg)
* Have received chondrocyte transplants in any lower extremity joint
* Use oral or topical COXIBs, calcitonin or immunosuppressive drugs

Primary outcomes:
measure: Cartilage Volume Loss of the Lateral Compartment
timeFrame: 12 months (Day 364) and 24 months (Day 728)
Secondary outcomes:
measure: Cartilage Volume Loss of the Global Knee
timeFrame: 12 months (Day 364) and 24 months (Day 728)
measure: Cartilage Volume in the Medial Compartment
timeFrame: 12 months (Day 364) and 24 months (Day 728)
measure: Synovial Membrane Thickness
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Bone Marrow Lesions Score
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Synovial Fluid Volume
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Percentage of Participants With the Presence of Extrusion in the Meniscus
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Visual Analog Scale (VAS)
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: WOMAC Pain Subscale
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: WOMAC Stiffness Subscale
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: WOMAC Function Subscale
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Short Form (SF-36) Health Survey
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Percentage of Participants With Presence of Joint Swelling and Effusion
timeFrame: Baseline, 12 months (Day 364) and 24 months (Day 728)
measure: Use of Acetaminophen
timeFrame: 3 months (Day 91), 6 momnths (Day 182), 12 months (Day 364), 18 monts (Day 546) and 24 months (Day 728)
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Osteoarthritis Research Unit, University of Montreal Hospital Research Centre (CRCHUM)
state: Quebec
city: Montréal
country: Canada
facility: Institut de Rhumatologie de Montréal
state: Quebec
city: Québec
country: Canada
facility: Groupe de Recherche en rhumatologie et maladies osseoues
state: Quebec
city: Sante Foi
country: Canada
facility: Centre de Rhumatologie St. Louis
state: Quebec
city: Trois-Rivières
country: Canada
facility: Centre de Recherche musculo-squellettique
state: Quebec
Study officials:
affiliation: Principal Author
name: Jean-Pierre Pelletier, MD
role: STUDY_CHAIR
References:
citation: Martel-Pelletier J, Raynauld JP, Mineau F, Abram F, Paiement P, Delorme P, Pelletier JP. Levels of serum biomarkers from a two-year multicentre trial are associated with treatment response on knee osteoarthritis cartilage loss as assessed by magnetic resonance imaging: an exploratory study. Arthritis Res Ther. 2017 Jul 20;19(1):169. doi: 10.1186/s13075-017-1377-y.
citation: Pelletier JP, Raynauld JP, Beaulieu AD, Bessette L, Morin F, de Brum-Fernandes AJ, Delorme P, Dorais M, Paiement P, Abram F, Martel-Pelletier J. Chondroitin sulfate efficacy versus celecoxib on knee osteoarthritis structural changes using magnetic resonance imaging: a 2-year multicentre exploratory study. Arthritis Res Ther. 2016 Nov 3;18(1):256. doi: 10.1186/s13075-016-1149-0.