Pharmacogenomics of Antiplatelet Response - II (PARes-II)

Johns Hopkins University

Status and phase

Completed

Phase 4

Conditions

Atherothrombosis

Treatments

Drug: Aspirin

Study type

Interventional

Funder types

Other

Identifiers

NCT01894555

K23HL105897 (U.S. NIH Grant/Contract)

K23HL105897-PARes-II

Details and patient eligibility

About

This clinical trial is examining the effect of 4-week aspirin therapy on platelet transcriptome in persons at high-risk for myocardial infarction or stroke due to family history of early-onset coronary artery disease.

Full description

Platelet aggregation can initiate thrombosis on ulcerated arterial plaques resulting in acute coronary syndrome (ACS). There is large variation in platelet aggregation between individuals. As the genetic message to the cell machinery is conveyed through its transcriptome, we hypothesize that much of the variability in platelet function can be explained by transcriptome changes including differences in gene or isoform expression, altered splicing events, or allele-specific expression. Moreover, aspirin modifies gene expression in several cells, but whether it also affects platelet transcriptome has not yet been studied. Our goal is to characterize the platelet transcriptome and identify genes that are up- or down-regulated after 4-week aspirin therapy. A major strength of our study is that it enrolls individuals from European Americans and African Americans and thus will have the ability to study similarities and differences between the two. The study will produce innovative comparative genomic/platelet phenotype data and will provide a potential pharmacogenomic and diagnostic template for the future discovery of novel antiplatelet regimens to prevent thrombosis-related cardiovascular disease events.

Enrollment

33 patients

Sex

All

Ages

45 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Participants from the GeneSTAR cohort
Unaffected with no overt coronary artery disease or serious vascular event (stroke or peripheral vascular disease diagnosis
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).