CES1 Carriers in the PAPI Study

Coronary Artery Disease Clinical Trial

Official title:

Enrichment of CES1 Carriers in the Pharmacogenomics Anti-Platelet Intervention Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03188705
• Other study ID #: HP-00075567
• Status: Completed
• Phase: Phase 4
• Start date: October 14, 2019
• Est. completion date: January 17, 2020

Study information

• Verified date: May 2023
• Source: University of Maryland, Baltimore
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study builds, in part, upon preliminary results generated as part of the Pharmacogenomics Anti-Platelet Intervention (PAPI) Study (NCT00799396). The purpose of this investigation is to assess the impact of genetic variation in the carboxylesterase 1 (CES1) on response to clopidogrel as well as dual antiplatelet therapy (i.e. clopidogrel and aspirin), as assessed by ex vivo platelet aggregometry, in healthy Amish individuals. The investigators hypothesize that participants who carry alleles that modify the activity or expression of CES1 will have altered response to clopidogrel as well as dual antiplatelet therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: January 17, 2020
• Est. primary completion date: January 17, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 20 Years and older

Eligibility

Inclusion Criteria:

• Age 20 years or older

• Of Old Order Amish descent

Exclusion Criteria:

• Currently pregnant or less than 6 months have passed since delivery

• Currently breast feeding

• Has a history of a bleeding disorder or major spontaneous bleed, such as peptic ulcer, epistasis, or intracranial bleed

• Has severe hypertension, defined by a blood pressure above 160/95 mm Hg

• Takes medications that would affect the outcome(s) to be measured and cannot willingly and safely, in the opinion of the treating physician and study physician, discontinue these medications for 1 week prior to protocol initiation

• Is taking vitamins or other supplements and is unwilling to discontinue use for at least 1 week prior to study

• Has a coexisting malignancy

• Has a creatinine level greater than 2.0 mg/dl, aspartate transaminase (AST) or alanine transaminase (ALT) greater than two times the upper limit of normal, hematocrit less than 32%, or a thyroid-stimulating hormone (TSH) less than 0.4 or greater than 5.5 mIU/L

• Has a bleeding disorder or history of gastrointestinal bleeding or other major bleeding episode

• Is currently taking aspirin, clopidogrel, or anti-coagulants, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place the participant at increased risk from withdrawal of these medications 14 days prior to protocol initiation

• History of unstable angina, heart attack, angioplasty (including stent placement), coronary artery bypass surgery, atrial fibrillation, stroke or transient ischemic attacks, diabetes, or deep vein thrombosis or other thrombosis

• Has polycythemia, or thrombocytosis, defined by a platelet count greater than 500,000

• Has thrombocytopenia, defined by a platelet count less than 75,000

• Has had surgery within the last 6 months

• Has an aspirin or clopidogrel allergy

Related Conditions & MeSH terms

• Artery Occlusion
• Aspirin Sensitivity
• Cardiovascular Diseases
• Clopidogrel, Poor Metabolism of
• Coronary Artery Disease
• Coronary Disease
• Heart Diseases
• Ischemia
• Myocardial Ischemia
• Platelet Dysfunction
• Platelet Thrombus

Intervention

Drug:
• Clopidogrel
Participants will receive 300 mg of clopidogrel on the first day, then 75 mg per day for the next 6 days. Measures of pharmacodynamics will be assessed pre- and post-drug administration.
• Aspirin
Participants will receive a single dose of 324 mg aspirin on the last day of clopidogrel administration.

Locations

Country	Name	City	State
United States	Amish Research Clinic	Lancaster	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Maryland, Baltimore

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Platelet Function in Response to Clopidogrel	Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation in response to ADP (20 ug/ml) or collagen (5 ug/ml). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline (recorded as a percentage) minus the maximum platelet aggregation value obtained after clopidogrel administration but before aspirin administration (also recorded as percentage). Thus, values recorded below represent a percentage change.	Measured at baseline and after 8 days of clopidogrel treatment
Primary	Changes in Platelet Function in Response to Clopidogrel Plus Aspirin	Baseline minus post clopidogrel/post-aspirin platelet rich plasma (PRP) maximum aggregation in response to ADP (20 ug/ml) or collagen (5 ug/ml). Maximum platelet aggregation is recorded by the platelet aggregometer as a percentage. Data shown below represent the maximum platelet aggregation value obtained at baseline (recorded as a percentage) minus the maximum platelet aggregation value obtained after clopidogrel and aspirin administration (also recorded as percentage). Thus, values recorded below represent a percentage change.	Measured at baseline and after 8 days clopidogrel administration plus 1 day of aspirin treatment