CES1 Carriers in the PAPI Study

NCT ID: NCT03188705

Last Updated: 2023-06-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 6 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-14
• Study Completion Date: 2020-01-17

Brief 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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Overall Cohort

Participants will receive clopidogrel treatment alone (300 mg loading dose followed by 75 mg/d for 6 days), followed by clopidogrel (75 mg) plus aspirin (324 mg) treatment on day 8.

Group Type: EXPERIMENTAL

Clopidogrel

Intervention Type: DRUG

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

Intervention Type: DRUG

Participants will receive a single dose of 324 mg aspirin on the last day of clopidogrel administration.

Interventions

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.

Intervention Type: DRUG

Aspirin

Participants will receive a single dose of 324 mg aspirin on the last day of clopidogrel administration.

Intervention Type: DRUG

Other Intervention Names

Plavix

Eligibility Criteria

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

• Minimum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Maryland, Baltimore

OTHER

Sponsor Role: lead

Responsible Party

Joshua Lewis

Associate Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joshua P Lewis, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Locations

Amish Research Clinic

Lancaster, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HP-00075567

Identifier Type: -

Identifier Source: org_study_id