Clinical trial NCT01894555: Pharmacogenomics of Antiplatelet Response - II (PARes-II)
Official title: Pharmacogenomics of Antiplatelet Response - II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Atherothrombosis
Keywords: Platelet Transcriptome
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Lead sponsor: Johns Hopkins University
Sponsor class: OTHER
First posted: 2013-07-10
Enrollment: 33
Sex: ALL
Minimum age (years): 45
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed 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.

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
* 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).

Primary outcomes:
measure: Changes in Platelet Transcriptome
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: Johns Hopkins University School of Medicine
state: Maryland
Study officials:
affiliation: Johns Hopkins School of Medicine
name: Rehan Qayyum, MD
role: PRINCIPAL_INVESTIGATOR
References: