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CES1 Carriers in the PAPI Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03188705
Recruitment Status : Enrolling by invitation
First Posted : June 15, 2017
Last Update Posted : November 3, 2020
Information provided by (Responsible Party):
Joshua Lewis, 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.

Condition or disease Intervention/treatment Phase
Heart Diseases Coronary Disease Coronary Artery Disease Cardiovascular Diseases Myocardial Ischemia Artery Occlusion Aspirin Sensitivity Clopidogrel, Poor Metabolism of Platelet Dysfunction Platelet Thrombus Drug: Clopidogrel Drug: Aspirin Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: The investigators will enroll 50 healthy Amish participants who have been identified through existing whole genome and exome sequencing along with bioinformatic approaches that have genetic variants that are predicted to significantly impact CES1 expression or catalytic function. Enrolled participants will undergo a two-stage intervention with clopidogrel (300 mg loading dose then 75 mg per day for the next 6 days), followed by clopidogrel (75 mg) plus aspirin 324 mg for 1 day. Platelet aggregation studies and other measures of platelet function will be performed before and after each intervention. In combination with previously collected data as part of the PAPI Study, the investigators will then characterize the impact of genetic variation in CES1 on clopidogrel and dual antiplatelet therapy response through single- and multi-variant association modeling.
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Enrichment of CES1 Carriers in the Pharmacogenomics Anti-Platelet Intervention Study
Actual Study Start Date : October 14, 2019
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: 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.
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.
Other Name: Plavix

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

Primary Outcome Measures :
  1. Changes in Platelet Function in Response to Clopidogrel [ Time Frame: Measured at baseline and after 8 days of clopidogrel treatment ]
    Baseline minus post clopidogrel/pre-aspirin platelet rich plasma (PRP) maximum aggregation

  2. Changes in Platelet Function in Response to Clopidogrel Plus Aspirin [ Time Frame: 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

Information from the National Library of Medicine

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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03188705

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United States, Pennsylvania
Amish Research Clinic
Lancaster, Pennsylvania, United States, 17602
Sponsors and Collaborators
University of Maryland, Baltimore
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Principal Investigator: Joshua P Lewis, PhD University of Maryland, College Park
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Responsible Party: Joshua Lewis, Assistant Professor of Medicine, University of Maryland, Baltimore Identifier: NCT03188705    
Other Study ID Numbers: HP-00075567
First Posted: June 15, 2017    Key Record Dates
Last Update Posted: November 3, 2020
Last Verified: November 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:


It is possible that deidentified data will be deposited into large public databases as per NIH data sharing policies (e.g. dbGAP, PharmGKB). Data to be shared would include, but not limited to, anthropometric data, study outcome data, and relevant covariate data used in statistical models of association. It is anticipated that data would be available after the completion of the trial. The data will be obtained from the participants and the study-related research procedures.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Joshua Lewis, University of Maryland, Baltimore:
Personalized Medicine
Additional relevant MeSH terms:
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Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Cardiovascular Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors