CES1 Carriers in the PAPI Study

University of Maryland Baltimore (UMB)

Status and phase: Completed; Phase 4

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

Treatments: Drug: Aspirin; Drug: Clopidogrel

Study type: Interventional

Funder types: Other

Identifiers

NCT03188705

HP-00075567

Details and patient eligibility

About

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.

Enrollment: 6 patients

Sex: All

Ages: 20+ years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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6 participants in 1 patient group

Overall Cohort

Experimental group

Description:

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.

Treatment:

Drug: Aspirin

Drug: Clopidogrel