Pharmacogenomics of Antiplatelet Response - I (PARes-I)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Rehan Qayyum, Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT01815008
First received: March 18, 2013
Last updated: September 5, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Platelet Aggregation
Platelet Transcriptome
Coronary Artery Disease
Drug: Clopidogrel
Drug: Aspirin
Phase 4

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: PHARMACOGENOMICS OF ANTI-PLATELET RESPONSE - I

Resource links provided by NLM:


Further study details as provided by Johns Hopkins University:

Primary Outcome Measures:
  • Difference in ADP-induced Platelet Aggregation [ Time Frame: at baseline and at 1 week ] [ Designated as safety issue: No ]
    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


Secondary Outcome Measures:
  • Difference in Arachidonic Acid-induced Platelet Aggregation [ Time Frame: At baseline and after 1-week ] [ Designated as safety issue: No ]
    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

  • Difference in Collagen-induced Platelet Aggregation [ Time Frame: At Baseline and at 1 week ] [ Designated as safety issue: No ]
    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

  • Changes in Platelet Transcriptome with Clopidogrel [ Time Frame: At baseline and at 1 week ] [ Designated as safety issue: No ]
    Platelet transcriptome will be examined before and after 1 week of therapy with clopidogrel and differences will be determined


Enrollment: 28
Study Start Date: October 2012
Study Completion Date: June 2014
Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Clopidogrel
Clopidogrel 75 mg daily by mouth for 1 week then Clopidogrel 75 mg daily with aspirin 81 mg daily
Drug: Clopidogrel
Clopidogrel 75 mg daily
Other Name: Plavix
Drug: Aspirin
Aspirin 81 mg daily

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.

  Eligibility

Ages Eligible for Study:   45 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  Contacts and Locations
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: NCT01815008

Locations
United States, Maryland
Johns Hopkins University School of Medicine
Baltimore, Maryland, United States, 21287
Sponsors and Collaborators
Johns Hopkins University
Investigators
Principal Investigator: Rehan Qayyum, MD Johns Hopkins University
  More Information

Additional Information:
No publications provided

Responsible Party: Rehan Qayyum, Assistant Professor of Medicine, Johns Hopkins University
ClinicalTrials.gov Identifier: NCT01815008     History of Changes
Other Study ID Numbers: K23HL105897-PARes-I
Study First Received: March 18, 2013
Last Updated: September 5, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Johns Hopkins University:
Platelet aggregation
Clopidogrel
Platelet transcriptome

Additional relevant MeSH terms:
Coronary Artery Disease
Myocardial Ischemia
Coronary Disease
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Aspirin
Clopidogrel
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 18, 2014