Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial.
BACKGROUND
Despite the high prevalence and global impact of knee osteoarthritis (KOA), current treatments are palliative. No disease modifying anti-osteoarthritic drug (DMOAD) has been approved. We recently demonstrated significant involvement of uric acid and activation of the innate immune response in osteoarthritis (OA) pathology and progression, suggesting that traditional gout therapy may be beneficial for OA. We therefore assess colchicine, an existing commercially available agent for gout, for a new therapeutic application in KOA.


METHODS
COLKOA is a double-blind, placebo-controlled, randomized trial comparing a 16-week treatment with standard daily dose oral colchicine to placebo for KOA. A total of 120 participants with symptomatic KOA will be recruited from a single center in Singapore. The primary end point is 30% improvement in total Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score at week 16. Secondary end points include improvement in pain, physical function, and quality of life and change in serum, urine and synovial fluid biomarkers of cartilage metabolism and inflammation. A magnetic resonance imaging (MRI) substudy will be conducted in 20 participants to evaluate change in synovitis. Logistic regression will be used to compare changes between groups in an intention-to-treat analysis.


CONCLUSIONS
The COLKOA trial is designed to evaluate whether commercially available colchicine is effective for improving signs and symptoms of KOA, and reducing synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. These biomarkers should provide insights into the underlying mechanism of therapeutic response. This trial will potentially provide data to support a new treatment option for KOA.


BACKGROUND
The trial has been registered at clinicaltrials.gov as NCT02176460 . Date of registration: 26 June 2014.
Duke NUS Graduate Medical School, Singapore, Singapore. katyccc@hotmail.com.|Department of Rheumatology & Immunology, Singapore General Hospital, Singapore, Singapore. katyccc@hotmail.com.
Ying-Ying
YY
Leung
Duke NUS Graduate Medical School, Singapore, Singapore. Julian.thumboo@sgh.com.sg.|Department of Rheumatology & Immunology, Singapore General Hospital, Singapore, Singapore. Julian.thumboo@sgh.com.sg.
Julian
J
Thumboo
Department of Diagnostic Radiology, Singapore General Hospital, Singapore, Singapore. steven.wong@sgh.com.sg.
Bak Siew
BS
Wong
Duke NUS Graduate Medical School, Singapore, Singapore. benhaaland@hotmail.com.
Ben
B
Haaland
Duke NUS Graduate Medical School, Singapore, Singapore. ctebal@nccs.com.sg.
Balram
B
Chowbay
Duke NUS Graduate Medical School, Singapore, Singapore. bibhas.chakraborty@duke-nus.edu.sg.
Bibhas
B
Chakraborty
Department of Orthopaedic Surgery, Singapore General Hospital, Singapore, Singapore. tan.mann.hong@sgh.com.sg.
Mann Hong
MH
Tan
The Duke Molecular Physiology Institute and Division of Rheumatology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA. vbk@duke.edu.
Virginia B
VB
Kraus
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D002985:Clinical Protocols; D003078:Colchicine / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D057194:Intention to Treat Analysis; D007719:Knee Joint / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology / Q000523:psychology; D010147:Pain Measurement; D011788:Quality of Life; D020127:Recovery of Function; D012107:Research Design; D012846:Singapore; D011795:Surveys and Questionnaires; D013582:Synovial Fluid / Q000276:immunology; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D018836:Inflammation Mediators; D003078:Colchicine