Colchicine for the Treatment of Osteoarthritis of the Knee

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IV, Randomized, Double-Blind, Placebo-Controlled, Single-Center Study of the Effects of Colchicine on Pain and Inflammation in Subjects With Knee Osteoarthritis

Conditions
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Osteoarthritis, Osteo Arthritis Knee

Intervention / Treatment
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* Drug: Colchicine 0.8 mg or 0.6 mg orally once daily
* Drug: Placebo oral capsule


Participation Criteria
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Eligibility Criteria
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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).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo in capsule identical to study drug | Drug: Placebo oral capsule<br>* Placebo 0.8 mg or 0.6 mg orally once daily for 3 months<br>|
| Experimental: Colchicine<br>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. | Drug: Colchicine 0.8 mg or 0.6 mg orally once daily<br>* Colchicine 0.8 mg orally once daily for 1.5 months, and then 0.6 mg once daily for the remainder of the time (1.5 months)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in mean changes of VAS pain scores between treatment groups | The VAS scale asks patients to rate the pain that they've had in each knee during the past 30 days on a scale of 0-10, where 0 means No pain and 10 means Pain as bad as you can imagine. | 3 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean changes and absolute differences in the Knee Injury and Osteoarthritis Outcome Score (KOOS) for pain | The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. | 3 Months | 
| mean changes of KOOS stiffness | The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. | 3 Months | 
| mean absolute doses and changes in dosage of acetaminophen or other medications used for pain between and within the groups at baseline and 3 months. |  | 3 Months | 
| mean changes of KOOS physical function | The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. | 3 Months | 
| mean changes between total KOOS scores between and within the groups at 3 months. | The KOOS's five patient-relevant dimensions are scored separately: Pain (nine items); Symptoms (seven items); ADL Function (17 items); Sport and Recreation Function (five items); Quality of Life (four items). A Likert scale is used and all items have five possible answer options scored from 0 (No problems) to 4 (Extreme problems) and each of the five scores is calculated as the sum of the items included. | 3 Months |