CES1 Carriers in the PAPI Study

Phase 4

Completed

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

• Registration Number: NCT03188705
• Lead Sponsor: University of Maryland, Baltimore

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-06-14
• Study First Submitted QC: 2017-06-14
• Study First Posted: 2017-06-15
• Study Start: 2019-10-14
• Primary Completion: 2020-01-17
• Study Completion: 2020-01-17
• Results First Submitted: 2023-04-13
• Status Verified: 2023-05
• Results First Submitted QC: 2023-05-23
• Last Update Submitted: 2023-05-23
• Results First Posted: 2023-06-15
• Last Update Posted: 2023-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 6

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Overall Cohort	Clopidogrel	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.
Overall Cohort	Aspirin	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.

Primary Outcome Measures

Name	Time	Method
Changes in Platelet Function in Response to Clopidogrel	Measured at baseline and after 8 days of clopidogrel treatment	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.
Changes in Platelet Function in Response to Clopidogrel Plus Aspirin	Measured at baseline and after 8 days clopidogrel administration plus 1 day of aspirin treatment	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.

Trial Locations

Locations (1)

Amish Research Clinic; 🇺🇸 Lancaster, Pennsylvania, United States