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Pharmacogenomics of Antiplatelet Response - I (PARes-I)

Primary Purpose

Platelet Aggregation, Platelet Transcriptome, Coronary Artery Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Clopidogrel
Aspirin
Sponsored by
Johns Hopkins University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Platelet Aggregation focused on measuring Platelet aggregation, Clopidogrel, Platelet transcriptome

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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
  • 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).

Sites / Locations

  • Johns Hopkins University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Clopidogrel

Arm Description

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

Outcomes

Primary Outcome Measures

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. Higher impedance represent higher platelet aggregation.

Secondary Outcome Measures

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
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
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

Full Information

First Posted
March 18, 2013
Last Updated
November 10, 2016
Sponsor
Johns Hopkins University
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1. Study Identification

Unique Protocol Identification Number
NCT01815008
Brief Title
Pharmacogenomics of Antiplatelet Response - I
Acronym
PARes-I
Official Title
PHARMACOGENOMICS OF ANTI-PLATELET RESPONSE - I
Study Type
Interventional

2. Study Status

Record Verification Date
November 2016
Overall Recruitment Status
Completed
Study Start Date
October 2012 (undefined)
Primary Completion Date
June 2014 (Actual)
Study Completion Date
June 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Johns Hopkins University

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Platelet Aggregation, Platelet Transcriptome, Coronary Artery Disease
Keywords
Platelet aggregation, Clopidogrel, Platelet transcriptome

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Clopidogrel
Arm Type
Experimental
Arm Description
Clopidogrel 75 mg daily by mouth for 1 week then Clopidogrel 75 mg daily with aspirin 81 mg daily
Intervention Type
Drug
Intervention Name(s)
Clopidogrel
Other Intervention Name(s)
Plavix
Intervention Description
Clopidogrel 75 mg daily
Intervention Type
Drug
Intervention Name(s)
Aspirin
Intervention Description
Aspirin 81 mg daily
Primary Outcome Measure Information:
Title
Difference in ADP-induced Platelet Aggregation
Description
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. Higher impedance represent higher platelet aggregation.
Time Frame
at baseline and at 1 week
Secondary Outcome Measure Information:
Title
Difference in Arachidonic Acid-induced Platelet Aggregation
Description
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
Time Frame
At baseline and after 1-week
Title
Difference in Collagen-induced Platelet Aggregation
Description
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
Time Frame
At Baseline and at 1 week
Title
Changes in Platelet Transcriptome With Clopidogrel
Description
Platelet transcriptome will be examined before and after 1 week of therapy with clopidogrel and differences will be determined
Time Frame
At baseline and at 1 week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Rehan Qayyum, MD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins University School of Medicine
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.genestarstudy.com/
Description
GeneSTAR Research Program

Learn more about this trial

Pharmacogenomics of Antiplatelet Response - I

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