Mechanistic Effects of Colchicine in Patients With Myocardial Infarction

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)

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.