Revisiting the Mechanism of the Anti-inflammatory Effect of Colchicine

Study Overview
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Brief Summary
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We are doing this research study to better understand the mechanism of action of colchicine, a drug commonly prescribed for gout. Precisely, we aim to evaluate the effect of colchicine on a specific protein (GDF15) blood levels at different timepoints after its administration. This research study will compare GDF15 blood levels after the administration of colchicine or placebo. The placebo looks exactly like colchicine but contains no active drug. During this study, participants may get a placebo instead of colchicine. Placebos are used in research studies to see if the results are due to the study drug or due to other reasons.

Detailed Description
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This will be a randomized, placebo-controlled, double-blind, pilot study evaluating the effect of a single FDA-approved dose of colchicine in healthy adults on plasma GDF15 levels. Randomization will be stratified by sex as this may be a factor influencing GDF15 levels. On Day 1, subjects will be admitted on the CCI 9A unit early in the morning, 30 minutes before the study drug administration. They will be asked to fast from midnight before the dose until 2 hours after. Water is allowed during the fasting period. Baseline blood tests will be drawn and a peripheral line will be left in place for further blood draws. A dose of either colchicine or placebo will be administered. Blood samples will be drawn at 2, 4, 6, 8, 10 and 12 hours. The patient will be discharged home after the last blood draw and the removal of the peripheral line. Two other blood draws will be performed using standard procedures at 24 and 48 hours post study drug administration at the research clinic

Official Title
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Revisiting the Mechanism of the Anti-inflammatory Effect of Colchicine

Conditions
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Colchicine Mechanism of Action

Intervention / Treatment
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* Drug: Colchicine Tablets
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant able to understand and sign the informed consent of the study Healthy male or female aged from 18 to 50 years. Participant considered healthy after evaluation such as medical history and screening laboratories. Exclusion Criteria: Pregnant or lactating women Use of colchicine within 28 days prior to study drug administration. Renal insufficiency (GFR < 50 mL/min) Use of any drug or product known to interact with colchicine including CYP3A4 and/or P-glycoprotein (P-gp) inhibitors in the 14 days prior study drug administration, such as atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, verapamil, cyclosporine and ranolazine. Significant consumption of grapefruit juice can also inhibit CYP3A4. Interactions may also be seen with fibrates (e.g., gemfibrozil), HMG-CoA reductase inhibitors (statins) and digoxin. History of colchicine allergy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Stratified randomization according to sex will be performed. Each group will be randomized to receive colchicine or placebo.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Male<br>Participants in this group will be randomized to receive either a single dose of colchicine (1.8mg administered over 1 hour in the form of tablets) or placebo. | Drug: Colchicine Tablets<br>* 1.8mg of Colchicine given over 1 hour (1.2 mg followed by 0.6 mg 1 hour later)<br>Drug: Placebo oral tablet<br>* Placebo given over 1 hour (first tablet followed by second tablet 1 hour later)<br>|
| Experimental: Female<br>Participants in this group will be randomized to receive either a single dose of colchicine (1.8mg administered over 1 hour in the form of tablets) or placebo. | Drug: Colchicine Tablets<br>* 1.8mg of Colchicine given over 1 hour (1.2 mg followed by 0.6 mg 1 hour later)<br>Drug: Placebo oral tablet<br>* Placebo given over 1 hour (first tablet followed by second tablet 1 hour later)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma GDF15 levels | The primary endpoint will be the plasma GDF15 level before and at different timepoints after colchicine administration. Plasma GDF-15 level will be determined using an enzyme immunoassay (EIA) testing. | Before product administration and 2, 4, 6 ,8, 10,12, 24 and 48 hours after product administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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pharmacology