Clinical trial NCT02995512: Mechanistic Effects of Colchicine in Patients With Myocardial Infarction
Official title: 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
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Myocardial Infarction
Keywords: myocardial infarction
colchicine
anti-inflammatory
Lead sponsor: NYU Langone Health
Sponsor class: OTHER
First posted: 2016-12-16
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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)

Eligibility criteria: 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.

Primary outcomes:
measure: Number of neutrophils adherent to TNFα-stimulated endothelial cells
timeFrame: 1 Day
Secondary outcomes:
measure: Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR
timeFrame: 1 Day
measure: Expression of adhesion molecules on the surface of neutrophils assessed via flow cytometry
timeFrame: 1 Day
measure: Measures of neutrophil metabolism (e.g. O2 consumption)
timeFrame: 1 Day
Other outcomes:
Locations:
Study officials:
affiliation: NYU Langone Health
name: Binita Shah, MD
role: PRINCIPAL_INVESTIGATOR
References: