Colchicine for the Treatment of Osteoarthritis of the Knee

Phase 4

Completed

Conditions: Osteoarthritis
Osteo Arthritis Knee

Interventions: Drug: Placebo oral capsule
Drug: Colchicine 0.8 mg or 0.6 mg orally once daily

Registration Number: NCT03913442

Lead Sponsor: NYU Langone Health

Brief Summary: This prospective, double-blinded, placebo-controlled, randomized trial will enroll 120 SKOA subjects at the NYU Center for Musculoskeletal Care. Patients meeting entry criteria will be randomized 1:1 to treatment with colchicine or placebo daily for 3 months. Subjects will have detailed evaluation of standardized clinical pain outcomes, candidate peripheral blood biomarkers, baseline knee radiographs as well as MSK-US, and a subset will undergo evaluation of their synovial fluid.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 120

Inclusion Criteria

Are 40 years old or older
Continue to experience frequent knee symptoms as defined above
Have KL grade 2 or 3 on their last knee radiograph done for the parent study
Have an estimated glomerular filtration rate (eGFR) > 30 ml/min (MDRD equation) and liver transaminases < 2x the upper limit of normal
Have a BMI ≤ 32 at the time of enrollment
Agree to be randomized to take colchicine or placebo daily for 3 months

Exclusion Criteria

Have received hyaluronic acid or corticosteroid steroid injection within the past 3 months
Have a diagnosis of gout/pseudogout or other inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, reactive arthritis, spondyloarthropathy etc).
Have a diagnosis of diabetes mellitus, chronic infectious disease, congestive heart failure, non-cutaneous cancer within the past 5 years
Plan on undergoing total knee replacement within the next 3 months
Be using any medication that is a strong CYP3A4 inhibitor whose metabolism may interact with colchicine (e.g., certain protease inhibitors, certain azole antifungal agents, clarithromycin).

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo oral capsule	Placebo in capsule identical to study drug
Colchicine	Colchicine 0.8 mg or 0.6 mg orally once daily	0.6 or 0.8 mg orally once daily. Because recent studies suggest that a dose of 0.6mg may be sufficient for chronic inflammatory suppression and may reduce the already low risk of toxicity of 0.8mg, for the remainder (second half) of the study the dosage will be switched from 0.8mg to a 0.6mg dose to allow comparison of the two doses.

Primary Outcome Measures

Name	Time	Method
Change in Visual Analog Scale (VAS) Pain Score	Baseline, 3 Months	VAS is a tool widely used to measure pain. A patient is asked to indicate his/her perceived pain intensity (most commonly) along a 10 mm horizontal line, and this rating is then measured from the left edge (=VAS score). The total score range is 0 (no pain) to 10 (worst pain imaginable); the higher the score, the worse the pain.

Secondary Outcome Measures

Name	Time	Method
Change in the Knee Injury and Osteoarthritis Outcome Score (KOOS) Pain Score	Baseline, 3 Months	The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The KOOS Pain Score refers to a specific subscale within the KOOS questionnaire that measures the severity of knee pain experienced by a patient, consisting of nine questions where each response is scored on a scale from 0 (no pain) to 4 (extreme pain), with a higher score indicating greater pain intensity; the overall pain score is then calculated as a percentage of the maximum possible score, where 0 represents the worst possible pain and 100 represents no pain at all.
Change in the KOOS Stiffness Score	Baseline, 3 Months	The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). Each item on the KOOS is scored on a scale from 0 (no problems) to 4 (extreme problems), and then the scores are calculated to generate a final score between 0 and 100. The KOOS stiffness score is a percentage from 0 to 100 that measures how much stiffness a patient experiences in their knee. A score of 0 indicates the most stiffness, while a score of 100 indicates no stiffness.
Change in the KOOS Physical Function Score	Baseline, 3 Months	The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Physical Function items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems. The scores for each dimension are then transformed to a scale from 0 to 100, where 0 represents extreme problems with knee function and 100 indicates no problems at all.
Change in the KOOS Quality of Life Score	Baseline, 3 Months	The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). A KOOS Quality of Life score ranges from 0 to 100, where 0 represents the worst possible knee-related quality of life and 100 indicates no problems at all. A higher score indicates better quality of life related to the knee.
Change in the KOOS Sports and Recreational Activities	Baseline, 3 Months	The KOOS's five patient-relevant dimensions are scored separately: Pain (9 items); Symptoms/Stiffness (7 items); Function, Daily Living (17 items); Function, Sports and Recreational Activities (5 items); Quality of Life (4 items). The KOOS Sports and Recreational Activities 9 items are scored on a Likert scale from 0 to 4, with 0 indicating no problems and 4 indicating extreme problems relating to sports and recreational activities. The scores are then transformed to a scale from 0 to 100, with 100 indicating no knee problems with sports and recreational activities and 0 indicating extreme knee problems with sports and recreational activities .
Change in the KOOS Total Score	Baseline, 3 Months	The KOOS survey is comprised of 42 questions. The questions are divided into 5 sub-categories: symptoms/stiffness (7 questions), pain (9 questions), function/daily living (17 questions), function/sports and recreational activities (5 questions), and quality of life (4 questions). The total range for each sub-category is 0-100, making the total range for the whole survey 0-500. The higher the score, the worse the symptoms and pain/ higher difficulty in function.
Number of Participants Who Used Acetaminophen or Other Medications for Pain	3 Months
Change in Number of Participants Who Used Acetaminophen or Other Medications for Pain	6 weeks, 3 months
Change in Inflammatory Plasma Marker: Interleukin-1 Receptor Antagonist (IL-1Ra)	Baseline, 3 months
Change in Inflammatory Plasma Marker: Prostaglandin E2 (PGE2)	Baseline, 3 months
Change in Musculoskeletal Ultrasound (MSK-US)-Measured Effusion	Baseline, 3 months	Size of effusion is measured as millimeters
Change in Rates of Crystal Deposition (Urate, Calcium) on MSK-US	Baseline, 3 months
Change in Inflammatory Plasma Marker: Highly Sensitive C-reactive Protein (hsCRP)	Baseline, 3 months
Change in Inflammatory Plasma Marker: Uric Acid	Baseline, 3 months