Colchicine for Symptom and Inflammation in Knee Osteoarthritis

NCT02176460 | Completed Phase 2

• 1 other identifier: COL-01
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

Uric acid may be involved in the activation of the innate immune response in osteoarthritis (OA) pathology and progression. This suggests that traditional gout therapy may be beneficial for OA. Our goal therefore is to assess colchicine, an existing commercially available agent for gout, for a new therapeutic indication-knee OA. The investigators propose a randomized clinical trial (RCT) of 16 weeks' therapy with standard daily dose oral colchicine or placebo for knee OA. The investigators hypothesize that colchicine will block inflammasome mediated inflammation, thereby improve the signs and symptoms of OA, and reduce synovial fluid, serum and urine inflammatory and biochemical joint degradation biomarkers. This trial will potentially provide data to support a new treatment option for knee OA.

Conditions

Knee Osteoarthritis

Keywords

Knee Osteoarthritis; Double-blind; placebo-controlled; randomized; colchicine

Outcome Measures

Primary Outcomes (1)

• 30% improvement in total Western Ontario and McMaster Universities Arthritis Index (WOMAC) of the signal knee.

  The primary end point will be 30% improvement in total Western Ontario and McMaster Universities Arthritis Index (WOMAC) of the signal knee.

  baseline and week 16

Secondary Outcomes (8)

• change in WOMAC pain score and physical function score

  baseline and week 16

• change in Health Assessment Questionnaire (HAQ)

  baseline and week 16

• change in quality of life

  baseline and week 16

• quantify of rescue medication used

  baseline and week 16

• Change in Synovitis and cartilage morphology on Magnetic Resonance Imaging

  baseline and week 16

Other Outcomes (3)

• Other exploratory outcomes include treatment response of the other biomarker variables.

  baseline and week 16

• Colchicine pharmacogenetics: Cytochrome P450 (CYP3A4) and (CYP3A5) polymorphism

  baseline

• pharmacokinetics: Peak Plasma Concentration (Cmax) of colchicine

  baseline, week 1, week 4 and week 16

Study Arms (2)

colchicine

EXPERIMENTAL

0.5mg twice daily for 16 weeks

Drug: Colchicine

placebo tablet

PLACEBO COMPARATOR

1 tablet twice daily for 16 weeks

Drug: Placebo

Interventions

Colchicine DRUG

0.5mg twice daily for 16 weeks

Also known as: generic colchicine tablets (SIN 12490P)

colchicine

Placebo DRUG

1 tablet twice daily

Also known as: placebo tablet

placebo tablet

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Symptomatic knee OA meeting American College of Rheumatology (ACR) criteria
• Radiographic criteria for knee OA with Kellgren-Lawrence (KL) stage of ≥ 2 in at least one knee
• Response positive to the question "do you have pain, aching or stiffness of the knee on most days of the past month
• Score of ≥ 40 out of 100 on a visual analogue scale (VAS) for pain
• Age ≥ 21 years or above
• Male and female subjects and all ethnicities included
• Patients to agree to avoid consuming grapefruit and grapefruit juice while using colchicine
• Ability to provide informed consent

You may not qualify if:

• Exposure to a corticosteroid (either parenteral or oral) within 3 months prior to the study enrolment
• Knee arthroscopic surgery within 6 months prior to the study enrolment
• Known history of avascular necrosis, inflammatory arthritis (e.g. Rheumatoid Arthritis), Paget's disease, joint infection, periarticular fracture, neuropathic arthropathy, Reiter's syndrome, or gout involving the knee
• Contraindication to arthrocentesis (warfarin use, bleeding disorder, skin rash or skin infection of signal knee)
• Knee joint replacement;
• History of podagra, active gout or treatment for gout
• Pregnancy or lactation - women of childbearing potential will have serum pregnancy testing (ßHCG) at time of entry prior to any imaging studies (X-ray or MRI); female subjects of childbearing potential must agree to use some form of contraception during the 16 week trial and for 1 week after the end of the trial (over 6 half-life equivalents)
• Renal failure with serum creatinine \> 150mmol/L (1.7 mg/dL);
• Hepatic impairment defined by serum alanine transaminase (ALT) above the upper limit of normal for the clinical laboratory performing the screening test
• Muscle impairment defined by elevated serum creatine phosphokinase (CPK) above the upper limit of normal for the clinical laboratory performing the screening test
• Personnel directly affiliated with this study or their immediate family members (defined as a spouse, parent, child or sibling, whether biological or legally adopted)
• Current enrolment in or discontinued within the last 30 days from a clinical trial involving an off-label use of an investigational drug or device, or are concurrently enrolled in any other type of medical research judged to be scientifically or medically incompatible with this study
• Inability to understand and cooperate with the investigators or to give valid consent;
• Anticipation of need for joint replacement within 4 months of the start of the intervention;
• Current treatment with drugs known to inhibit Cytochrome 450(3A4) isoforms and/or P-glycoprotein (P-gp) that increase the risk of colchicine-induced toxic effects (see: http://www.fda.gov/Drugs/Drug-safety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/ucm174315.htm).

Sponsors & Collaborators

• Singapore General Hospital: lead
• Duke University: collaborator
• Duke-NUS Graduate Medical School: collaborator

Study Sites (1)

Singapore General Hospital

Singapore, 169608, Singapore

Location

Related Publications (2)

• Leung YY, Haaland B, Huebner JL, Wong SBS, Tjai M, Wang C, Chowbay B, Thumboo J, Chakraborty B, Tan MH, Kraus VB. Colchicine lack of effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): a randomized controlled trial. Osteoarthritis Cartilage. 2018 May;26(5):631-640. doi: 10.1016/j.joca.2018.01.026. Epub 2018 Feb 7.

  PMID: 29426008 DERIVED

• Leung YY, Thumboo J, Wong BS, Haaland B, Chowbay B, Chakraborty B, Tan MH, Kraus VB. Colchicine effectiveness in symptom and inflammation modification in knee osteoarthritis (COLKOA): study protocol for a randomized controlled trial. Trials. 2015 Apr 30;16:200. doi: 10.1186/s13063-015-0726-x.

  PMID: 25925674 DERIVED

MeSH Terms

Conditions

Osteoarthritis, Knee

Interventions

Colchicine

Condition Hierarchy (Ancestors)

Osteoarthritis; Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds

Study Officials

• Ying Y Leung, MBChB

  Singapore General Hospital

  PRINCIPAL INVESTIGATOR

• Virginia Kraus, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2014
• First Posted: June 27, 2014
• Study Start: October 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: April 15, 2016

Record last verified: 2016-04

Locations

SG (1)