Pharmacogenomics of Antiplatelet Response - I

Coronary Artery Disease Clinical Trial

— PARes-I  

Official title:

PHARMACOGENOMICS OF ANTI-PLATELET RESPONSE - I

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01815008
• Other study ID #: K23HL105897-PARes-I
• Status: Completed
• Phase: Phase 4
• First received: March 18, 2013
• Last updated: September 5, 2014
• Start date: October 2012
• Est. completion date: June 2014

Study information

• Verified date: September 2014
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: June 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years to 75 Years

Eligibility

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).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Myocardial Ischemia
• Platelet Aggregation
• Platelet Transcriptome

Intervention

Drug:
• Clopidogrel
Clopidogrel 75 mg daily
• Aspirin
Aspirin 81 mg daily

Locations

Country	Name	City	State
United States	Johns Hopkins University School of Medicine	Baltimore	Maryland

Sponsors (1)

Lead Sponsor	Collaborator
Johns Hopkins University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Difference in ADP-induced Platelet Aggregation	ADP-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined	at baseline and at 1 week	No
Secondary	Difference in Arachidonic Acid-induced Platelet Aggregation	Arachidonic Acid-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined	At baseline and after 1-week	No
Secondary	Difference in Collagen-induced Platelet Aggregation	Collagen-induced platelet aggregation will be measured using impedance aggregometry in whole blood before and after 1-week of clopidogrel. The difference between the baseline and after clopidogrel therapy will be determined	At Baseline and at 1 week	No
Secondary	Changes in Platelet Transcriptome with Clopidogrel	Platelet transcriptome will be examined before and after 1 week of therapy with clopidogrel and differences will be determined	At baseline and at 1 week	No

External Links

•   GeneSTAR Research Program