Colchicine for Symptom and Inflammation in Knee Osteoarthritis

• Register: ClinicalTrials.gov
• Last refreshed on: 25 April 2016
• Main ID: NCT02176460
• Date of registration: 26/06/2014
• Prospective Registration: No
• Primary sponsor: Singapore General Hospital
• Public title: Colchicine for Symptom and Inflammation in Knee Osteoarthritis
• Scientific title: A Randomized Controlled Trial of Colchicine for Symptom and Inflammation Modification in Knee Osteoarthritis
• Date of first enrolment: October 2013
• Target sample size: 109
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02176460
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
• Phase: Phase 2/Phase 3

Countries of recruitment

Singapore

Contacts

• Name: Virginia Kraus, MD, PhD
• Affiliation: Duke University

• Name: Ying Y Leung, MBChB
• Affiliation: Singapore General Hospital

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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

Exclusion Criteria:

- 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;

- Contraindication for magnetic resonance imaging (MRI) - this is exclusion only for
the subset of individuals selected for this imaging procedure;

- 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).

Inclusion can be considered after 14 day wash out of agents listed in the drug information
sheet, but only if treatment in the near future with one of these agents is not
anticipated. The clinical necessity for such treatments during the study will require
immediate discontinuation of the study drug and conversion of the patient to standard
care. However, the patient will remain on study and scheduled measurements taken. Analyses
will be performed on an intention-to-treat basis.



Age minimum: 21 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Knee Osteoarthritis

Intervention(s)

Drug: Colchicine

Drug: Placebo

Primary Outcome(s)

30% improvement in total Western Ontario and McMaster Universities Arthritis Index (WOMAC) of the signal knee. [Time Frame: baseline and week 16]

Secondary Outcome(s)

OMERACT-ORSI response criteria [Time Frame: week 16]

Change in Synovitis and cartilage morphology on Magnetic Resonance Imaging [Time Frame: baseline and week 16]

change in Health Assessment Questionnaire (HAQ) [Time Frame: baseline and week 16]

change in quality of life [Time Frame: baseline and week 16]

change in synovial fluid Interleukin-18, Interleukin-1ß, or tumor necrosis factor -a [Time Frame: baseline and week 16]

quantify of rescue medication used [Time Frame: baseline and week 16]

specific adverse event [Time Frame: from baseline to week 16]

change in WOMAC pain score and physical function score [Time Frame: baseline and week 16]

Secondary ID(s)

COL-01

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Duke University

Duke-NUS Graduate Medical School