Revisiting the Mechanism of the Anti-inflammatory Effect of Colchicine

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.

Study Overview

• Status: Recruiting
• Conditions: Colchicine Mechanism of Action
• Intervention / Treatment: Drug: Colchicine Tablets; Drug: Placebo oral tablet

Detailed Description

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

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lindsey Baden, MD; Phone Number: 978-VACCINE; Email: vaccines@partners.org
• Study Contact Backup: Name: Jessica Cauley; Phone Number: 6177325394; Email: jcauley@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 48 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Male; 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; 1.8mg of Colchicine given over 1 hour (1.2 mg followed by 0.6 mg 1 hour later); Drug: Placebo oral tablet; Placebo given over 1 hour (first tablet followed by second tablet 1 hour later)
Experimental: Female; 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; 1.8mg of Colchicine given over 1 hour (1.2 mg followed by 0.6 mg 1 hour later); Drug: Placebo oral tablet; Placebo given over 1 hour (first tablet followed by second tablet 1 hour later)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Harvard Medical School (HMS and HSDM)
• Investigators: Principal Investigator: Lindsey Baden, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Anticipated): April 1, 2023
• Study Completion (Anticipated): April 1, 2023

Study Registration Dates

• First Submitted: April 18, 2020
• First Submitted That Met QC Criteria: April 18, 2020
• First Posted (Actual): April 21, 2020

Study Record Updates

• Last Update Posted (Actual): March 16, 2022
• Last Update Submitted That Met QC Criteria: March 14, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: pharmacology
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 2020P000440

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Deidentified data will be made available upon request to the principal investigator following the publication of the primary manuscript.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No