Mechanistic Effects of Colchicine in Patients With Myocardial Infarction

Myocardial Infarction Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02995512
• Other study ID #: 16-01704
• Status: Withdrawn
• Phase: Phase 4
• Start date: May 1, 2017
• Est. completion date: September 12, 2018

Study information

• Verified date: April 2019
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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)

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: September 12, 2018
• Est. primary completion date: September 12, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Infarction
• Myocardial Infarction

Intervention

Drug:
• Colchicine 0.6 mg tablets
1.2 mg PO followed by 0.6 mg PO 1 hour later

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
New York University School of Medicine

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of neutrophils adherent to TNFa-stimulated endothelial cells	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day
Secondary	Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day
Secondary	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
Secondary	Measures of neutrophil metabolism (e.g. O2 consumption)	Metabolism of neutrophils will be measured using the Seahorse assay.	1 Day