Mechanistic Effects of Colchicine in Patients With Myocardial Infarction

Mechanistic Effects of Colchicine in Patients With Myocardial Infarction A Single Center Phase 4 Single Arm Open-label Study Evaluating the FDA-approved Drug, Colchicine, at the FDA-approved Gout Dose in Patients With Myocardial Infarction

The aim of this study is to determine the immuno-modulatory mechanistic effects of colchicine in patients with myocardial infarction (MI). Investigators hypothesize that colchicine exerts its anti-inflammatory properties by switching the metabolism of neutrophils, thereby reducing the expression of adhesion molecules responsible for their recruitment in MI.

Study Overview

• Status: Withdrawn
• Conditions: Myocardial Infarction
• Intervention / Treatment: Drug: Colchicine 0.6 mg tablets

Detailed Description

This is a pilot study to explore the mechanistic effects of colchicine in patients with MI. The study will be conducted sequentially in 3 parts:

1. Blood will be collected from up to 10 healthy volunteers for protocol development. (Group 1).
2. Blood will be collected from 20 MI patients within 24 hours of presentation at New York University (NYU) Langone Medical Center and Bellevue Hospital Center (BHC). Neutrophil adhesion to human aortic endothelial cells, quantitative expression of adhesion molecules on the surface of neutrophils, quantitative levels of adhesion molecules on neutrophils and endothelial cells, and neutrophil metabolism, using a Seahorse Analyzer will be evaluated pre- and post-addition of in vitro colchicine. (Group 2)
3. The standard low-dose loading regimen of colchicine (1.2 mg followed by 0.6 mg one hour later) will be administered to 20 patients with MI at BHC. Blood will be collected prior to drug administration, 2 to 3 hours after completion of the colchicine load, and 23 to 24 hours after the completion of the colchicine load. Neutrophil adhesion to human aortic endothelial cells, quantitative expression of adhesion molecules on the surface of neutrophils, quantitative levels of adhesion molecules on neutrophils and endothelial cells, and neutrophil metabolism will be evaluated pre- and post-addition of in vitro colchicine (exact markers will be determined based on the results of in viro studies above). (Group 3)

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age for the healthy volunteer subset.
• 18 years of age and within 24 hours of an MI for the MI subset.

Exclusion Criteria:

Subjects in all 3 groups will be excluded if they meet one of the following criteria

• history of myelodysplasia;
• Use of anti-inflammatory medications, with the exception of aspirin, within 5 half-lives;
• medications known to interact with colchicine;
• known creatinine clearance <30 cc/minute (severe kidney disease);
• pregnant; or
• Unable to consent.

MI subjects who will have oral colchicine administered will have the following additional exclusion criteria:

• history of intolerance to colchicine;
• acute or chronic symptoms of diarrhea within 72 hours prior to enrollment;
• hemoglobin <10 g/dL or clinical evidence of active bleeding during the study period.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Myocardial Infarction (MI) Patients	Drug: Colchicine 0.6 mg tablets; 1.2 mg PO followed by 0.6 mg PO 1 hour later

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of neutrophils adherent to TNFα-stimulated endothelial cells	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day
Expression of adhesion molecules on the surface of neutrophils assessed via flow cytometry	Measurements of L-selectin, CD11b, and active CD11b will be made via an Accuri C6 flow cytometer using standard antibodies on an aliquot of whole blood.	1 Day
Measures of neutrophil metabolism (e.g. O2 consumption)	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day

Collaborators and Investigators

• Sponsor: NYU Langone Health
• Investigators: Principal Investigator: Binita Shah, MD, NYU Langone Health

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): September 12, 2018
• Study Completion (Actual): September 12, 2018

Study Registration Dates

• First Submitted: December 14, 2016
• First Submitted That Met QC Criteria: December 14, 2016
• First Posted (Estimate): December 16, 2016

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 16, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: myocardial infarction; anti-inflammatory; colchicine
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: 16-01704

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No