Mechanistic Effects of Colchicine in Patients With Myocardial Infarction
Primary Purpose
Myocardial Infarction
Status
Withdrawn
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Colchicine 0.6 mg tablets
Sponsored by
About this trial
This is an interventional treatment trial for Myocardial Infarction focused on measuring myocardial infarction, colchicine, anti-inflammatory
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Myocardial Infarction (MI) Patients
Arm Description
Outcomes
Primary Outcome Measures
Number of neutrophils adherent to TNFα-stimulated endothelial cells
Metabolism of neutrophils will be measured using the Seahorse assay.
Secondary Outcome Measures
Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR
Metabolism of neutrophils will be measured using the Seahorse assay.
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.
Measures of neutrophil metabolism (e.g. O2 consumption)
Metabolism of neutrophils will be measured using the Seahorse assay.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02995512
Brief Title
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
2. Study Status
Record Verification Date
April 2019
Overall Recruitment Status
Withdrawn
Why Stopped
feasibility
Study Start Date
May 1, 2017 (Actual)
Primary Completion Date
September 12, 2018 (Actual)
Study Completion Date
September 12, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
NYU Langone Health
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
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:
Blood will be collected from up to 10 healthy volunteers for protocol development. (Group 1).
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)
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)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myocardial Infarction
Keywords
myocardial infarction, colchicine, anti-inflammatory
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Myocardial Infarction (MI) Patients
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Colchicine 0.6 mg tablets
Intervention Description
1.2 mg PO followed by 0.6 mg PO 1 hour later
Primary Outcome Measure Information:
Title
Number of neutrophils adherent to TNFα-stimulated endothelial cells
Description
Metabolism of neutrophils will be measured using the Seahorse assay.
Time Frame
1 Day
Secondary Outcome Measure Information:
Title
Levels of adhesion molecules on neutrophils and endothelial cells quantified using PCR
Description
Metabolism of neutrophils will be measured using the Seahorse assay.
Time Frame
1 Day
Title
Expression of adhesion molecules on the surface of neutrophils assessed via flow cytometry
Description
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.
Time Frame
1 Day
Title
Measures of neutrophil metabolism (e.g. O2 consumption)
Description
Metabolism of neutrophils will be measured using the Seahorse assay.
Time Frame
1 Day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Binita Shah, MD
Organizational Affiliation
NYU Langone Health
Official's Role
Principal Investigator
12. IPD Sharing Statement
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Mechanistic Effects of Colchicine in Patients With Myocardial Infarction
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