PARes-III: Pharmacogenomics of Antiplatelet Response

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02234427
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Arm: 1
• Duration (Months): 11
• Patients Per Site Per Month: 3.1

Study Details

Study Description

Brief Summary

This clinical trial will examine with effect of 2-week aspirin therapy on platelet gene expression in persons at high-risk of developing heart attacks due to family history of early-onset coronary artery disease

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis	Drug: Aspirin	Phase 4

Detailed Description

In this clinical trials we will select individuals from GeneSTAR cohort based o their platelet function. Equal number of individuals will be selected from each race and gender and from low or high platelet aggregation. We will have baseline platelet functions performed and baseline platelet gene expression examined. Participants will be given 2-week supply of aspirin(81 mg/daily) and will be examined at the end of 2-weeks with platelet aggregation studies and a repeat platelet gene-expression (using RNA-seq). The ultimate goal is to examine platelet gene expression differences due to aspirin and across different gender, race, platelet-aggregation groups.

Study Design

• Study Type: Interventional
• Actual Enrollment: 34 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Pharmacogenomics of Antiplatelet Response
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Apr 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aspirin	Drug: Aspirin; 2-week aspirin therapy (81mg/day)

Outcome Measures

Primary Outcome Measures

1. Differential Gene Expression [2-weeks]

   Differences in platelet transcriptome before and after 2-week aspirin therapy The expression levels of genes before aspirin therapy was compared with the expression level of the genes after aspirin therapy. The expression levels were measured using the FPKM unit (Fragments Per Kilobase of transcript per Million mapped reads). The gene with the highest difference (pre vs. post) in FPKM is being reported with name in the units area and the actual difference in the number area

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 45-75 years

• GeneSTAR participant

• No personal History of Coronary Artery Disease

• Women who are post-menopausal

• Women who are using a reliable method of contraception, such as history of tubal ligation, IUD or taking OCP

Exclusion Criteria:

• Taking aspirin prescribed by physician

• weight < 60 kg

• History of recent or current bleeding

• allergy to aspirin or history of adverse events to aspirin

• serious comorbid conditions (such as AIDS, active cancer)

• high blood pressure (>160/95)

• History of gastrointestinal ulcer/bleeding

• Mental incompetence to make decision to participate.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Johns Hopkins School of Medicine	Baltimore	Maryland	United States	21287

Sponsors and Collaborators

• Johns Hopkins University

Investigators

• Principal Investigator: Rehan Qayyum, MD, Johns Hopkins School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• GeneSTAR Research Program

Publications

None provided.

• Responsible Party: Rehan Qayyum, Assistant Professor, Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT02234427
• Other Study ID Numbers: PARes-III
• First Posted: Sep 9, 2014
• Last Update Posted: Jan 9, 2017
• Last Verified: Nov 1, 2016

• Keywords provided by Rehan Qayyum, Assistant Professor, Johns Hopkins University: aspirin, atherosclerosis
• Additional relevant MeSH terms: Atherosclerosis; Aspirin

Study Results

Participant Flow

Arm/Group Title	Aspirin
Arm/Group Description	Aspirin: 2-week aspirin therapy (81mg/day)
Period Title: Overall Study
STARTED	34
COMPLETED	33
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Aspirin
Arm/Group Description	Aspirin: 2-week aspirin therapy (81mg/day)
Overall Participants	34
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53.4 (10.3)
Gender (Count of Participants)
Female	17 50%
Male	17 50%
Race/Ethnicity, Customized (participants) [Number]
African Americans	17 50%
Caucasians	17 50%

Outcome Measures

1. Primary Outcome

Title	Differential Gene Expression
Description	Differences in platelet transcriptome before and after 2-week aspirin therapy The expression levels of genes before aspirin therapy was compared with the expression level of the genes after aspirin therapy. The expression levels were measured using the FPKM unit (Fragments Per Kilobase of transcript per Million mapped reads). The gene with the highest difference (pre vs. post) in FPKM is being reported with name in the units area and the actual difference in the number area
Time Frame	2-weeks

Outcome Measure Data

Analysis Population Description

The data were analyzed combining results from two studies (24 from this study and additional 33 individuals from study NCT01894555; total population size = 57) to improve the power to detect a difference. Same results are reported for the two studies. Note that the top most gene (HBG1) with the lowest p-value is being reported.

Arm/Group Title	Aspirin
Arm/Group Description	Aspirin: 2-week aspirin therapy (81mg/day)
Measure Participants	57
Mean (Standard Error) [FPKM for HBG1 Gene]	77.1 (19.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aspirin
	Comments	Null Hypothesis: There is no difference in gene expression before and after aspirin therapy
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.000005
	Comments	Above noted p-value is adjusted for multiple comparisons. Analysis was performed using the TopHat/Cufflinks pipeline. The differential expression algorithm uses a beta distribution and the overdispersion with a negative binomial distribution.
	Method	negative binomial
	Comments

Adverse Events

Arm/Group Title	Aspirin
Arm/Group Description	Aspirin: 2-week aspirin therapy (81mg/day)
All Cause Mortality
	Aspirin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Aspirin
	Affected / at Risk (%)	# Events
Total	0/34 (0%)
Other (Not Including Serious) Adverse Events
	Aspirin
	Affected / at Risk (%)	# Events
Total	0/34 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.