Revisiting the Mechanism of the Anti-inflammatory Effect of Colchicine

Sponsor

Brigham and Women's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04355585

Collaborator

Harvard Medical School (HMS and HSDM) (Other)

Enrollment

Location

Arms

34.8

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Colchicine Mechanism of Action	Drug: Colchicine Tablets Drug: Placebo oral tablet	Phase 1

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 Design

Study Type:

Interventional

Anticipated Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Stratified randomization according to sex will be performed. Each group will be randomized to receive colchicine or placebo.Stratified randomization according to sex will be performed. Each group will be randomized to receive colchicine or placebo.

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

This is a double-blind study in which investigators, participants, site personnel, and laboratory staff will be blinded during the study. Only the research pharmacy will have access to randomization and treatment assignments.

Primary Purpose:

Basic Science

Official Title:

Revisiting the Mechanism of the Anti-inflammatory Effect of Colchicine

Actual Study Start Date :

May 6, 2020

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

Plasma GDF15 levels [Before product administration and 2, 4, 6 ,8, 10,12, 24 and 48 hours after product administration]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Brigham and Women's Hospital	Boston	Massachusetts	United States	02115

Sponsors and Collaborators

Brigham and Women's Hospital
Harvard Medical School (HMS and HSDM)

Investigators

Principal Investigator: Lindsey Baden, MD, Brigham and Women's Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Lindsey R. Baden, MD, Principle Investigator, Brigham and Women's Hospital

ClinicalTrials.gov Identifier:

NCT04355585

Other Study ID Numbers:

2020P000440

First Posted:

Apr 21, 2020

Last Update Posted:

Mar 16, 2022

Last Verified:

Mar 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Keywords provided by Lindsey R. Baden, MD, Principle Investigator, Brigham and Women's Hospital

pharmacology

Additional relevant MeSH terms:

Colchicine

Study Results

No Results Posted as of Mar 16, 2022