Pharmacogenomics of Antiplatelet Response - I

NCT ID: NCT01815008

Last Updated: 2017-01-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 19 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-10-31
• Study Completion Date: 2014-06-30

Brief Summary

This clinical trial is examining the role of genetic polymorphism on the effect of clopidogrel (with or without aspirin) on platelet response in persons at high-risk for myocardial infarction or stroke due to family history of early-onset coronary artery disease.

Detailed Description

The main goal of this study is to explore the impact of the PEAR1 genetic variant (rs12041331) on responsiveness to clopidogrel. The investigators will further assess the role of other genetic variants in determining the response to single or dual anti-platelet therapy. Apparently healthy subjects (N= 2108) from high-risk families are being (a) identified from a proband with early-onset CAD and (b) genotyped on the Illumina 1 million platform, with imputation to 2.5 million single nucleotide polymorphisms. The investigators plan to characterize the variance in platelet aggregation to multiple agonists (ADP, collagen, and arachidonic acid) after 1-week therapy with clopidogrel in a high-risk subset of GeneSTAR subjects (N=100). The investigators further plan to determine the extent to which variants identified in the PEAR1 gene modify platelet responsiveness to inhibition by clopidogrel in this high-risk subset. In addition, the investigators aim is to determine the extent to which variants in other recently discovered genes, by themselves, and in combination with PEAR1, modify platelet responsiveness to clopidogrel alone and with aspirin in this high-risk subset. Lastly, the investigators also want to determine what changes in platelet mRNA are produced by aspirin alone and by aspirin with clopidogrel.

Conditions

Platelet Aggregation; Platelet Transcriptome; Coronary Artery Disease

Study Design

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

Study Groups

Clopidogrel

Clopidogrel 75 mg daily by mouth for 1 week then Clopidogrel 75 mg daily with aspirin 81 mg daily

Group Type: EXPERIMENTAL

Clopidogrel

Intervention Type: DRUG

Clopidogrel 75 mg daily

Aspirin

Intervention Type: DRUG

Aspirin 81 mg daily

Interventions

Clopidogrel

Clopidogrel 75 mg daily

Intervention Type: DRUG

Aspirin

Aspirin 81 mg daily

Intervention Type: DRUG

Other Intervention Names

Plavix

Eligibility Criteria

Inclusion Criteria

• Participants from the GeneSTAR cohort
• Unaffected with no overt coronary artery disease or serious vascular event (stroke or peripheral vascular disease diagnosis
• Presence of an occult coronary artery disease phenotype as defined by coronary artery calcium scores about the MESA (Multiethnic Study of Atherosclerosis) 75th percentile for age sex, and race or ≥ 1 stenoses in any of the major coronary arteries or main branches of > 50%, or coronary plaque volumetric scores above our own 75th percentile, or any combination on cardiac computed tomographic angiography (performed recently as part of the GeneSTAR study and present for all persons being recruited)/
• Presence of occult cerebrovascular disease defined as presence of white matter hyperintensities (WMH) thought to represent ischemic small vessel cerebrovascular disease, and /or the presence of lacunes (old small strokes), or the presence of an Atherosclerosis Risk in Communities Study (ARIC) silent stroke score on a visual analogue scales of 4 or more (on a scale of 0-9).
• Women who are postmenopausal.
• Women who use a reliable contraceptive method; a reliable contraceptive method will be defined as personal history of tubal ligation, ongoing use of intra-uterine device, or ongoing use of oral contraceptive pills.

Exclusion Criteria

• Presence of any CAD or stroke, transient ischemic attacks, peripheral arterial disease
• Persons taking aspirin, NSAIDS, or any anti-coagulants who are medically unable to stop them for a two week pre-trial
• A history of allergy to aspirin or clopidogrel
• Weight < 60kg
• Age < 45 and > 75 years of age
• A history of recent or any active bleeding
• Serious or current co-morbidity (AIDS, cancer)
• Pregnant women as determined by urine dipstick pregnancy test
• Any aneurysms on cranial magnetic resonance imaging/magnetic resonance angiography (obtained recently in the GeneSTAR participants)
• Blood pressure above >=159/95mmHg
• History of a gastric or duodenal ulcer, or significant gastrointestinal disease, like regional enteritis
• Mental incompetence to make a decision to participate (developmentally disabled, and persons with diagnosed psychiatric disorders-documented in primary care records).

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Johns Hopkins University

OTHER

Sponsor Role: lead

Responsible Party

Rehan Qayyum

Assistant Professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rehan Qayyum, MD

Role: PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Locations

Johns Hopkins University School of Medicine

Baltimore, Maryland, United States

Countries

United States

Related Links

http://www.genestarstudy.com/

GeneSTAR Research Program

Other Identifiers

K23HL105897

Identifier Type: NIH

Identifier Source: secondary_id

View Link

K23HL105897-PARes-I

Identifier Type: -

Identifier Source: org_study_id