CES1 Carriers in the PAPI Study


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Verified June 2017 by Joshua Lewis, University of Maryland

Sponsor:

Information provided by (Responsible Party):

Joshua Lewis, University of Maryland

ClinicalTrials.gov Identifier:

NCT03188705

First received: June 14, 2017

Last updated: June 14, 2017

Last verified: June 2017

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. We 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.

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

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Intervention Model Description:

We 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, we 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: No masking
Primary Purpose: Basic Science

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

Primary Outcome Measures:

Estimated Enrollment: 50
Anticipated Study Start Date: September 2017
Estimated Study Completion Date: September 2020
Estimated Primary Completion Date: September 2020 (Final data collection date for primary outcome measure)
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 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.

Ages Eligible for Study:   20 Years and older   (Adult, Senior)
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 their 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 other anti-coagulant, such as warfarin, heparin, or GPIIb/IIIa antagonists, and have conditions that might place them 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03188705

University of Maryland

Principal Investigator: Joshua P Lewis, PhD University of Maryland

Responsible Party: Joshua Lewis, Assistant Professor of Medicine, University of Maryland
ClinicalTrials.gov Identifier: NCT03188705     History of Changes
Other Study ID Numbers: HP-00075567
Study First Received: June 14, 2017
Last Updated: June 14, 2017
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description:

Yes

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.

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:

pharmacogenetics
carboxylesterase
Personalized Medicine

Additional relevant MeSH terms:

Cardiovascular Diseases
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Ischemia
Thrombosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Pathologic Processes
Embolism and Thrombosis
Clopidogrel
Ticlopidine
Aspirin
Platelet Aggregation Inhibitors
Purinergic P2Y Receptor Antagonists
Purinergic P2 Receptor Antagonists
Purinergic Antagonists
Purinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Fibrinolytic Agents
Fibrin Modulating Agents
Cytochrome P-450 CYP2C19 Inhibitors
Cytochrome P-450 Enzyme Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic

ClinicalTrials.gov processed this record on June 15, 2017