Pharmacogenomics of Antiplatelet Response - II (PARes-II)
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Aspirin Participants treated with aspirin - there is no control group. Participant's baseline will act as their control. |
Drug: Aspirin
81 mg daily for 4 weeks
|
Outcome Measures
Primary Outcome Measures
- Changes in Platelet Transcriptome [4 weeks]
Comparison of platelet transcriptome before aspirin therapy with platelet transcriptome after 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
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).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | 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 School of Medicine
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- K23HL105897-PARes-II
- K23HL105897
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Aspirin |
|---|---|
| Arm/Group Description | Participants treated with aspirin - there is no control group. Participant's baseline will act as their control. Aspirin: 81 mg daily for 4 weeks |
| Period Title: Overall Study | |
| STARTED | 33 |
| COMPLETED | 33 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Aspirin |
|---|---|
| Arm/Group Description | Participants treated with aspirin - there is no control group. Participant's baseline will act as their control. Aspirin: 81 mg daily for 4 weeks |
| Overall Participants | 33 |
| Age (years) [Mean (Standard Deviation) ] | |
| Mean (Standard Deviation) [years] |
50.6
(8.0)
|
| Gender (Count of Participants) | |
| Female |
15
45.5%
|
| Male |
18
54.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |
| African Americans |
22
66.7%
|
| Caucasians |
11
33.3%
|
Outcome Measures
| Title | Changes in Platelet Transcriptome |
|---|---|
| Description | Comparison of platelet transcriptome before aspirin therapy with platelet transcriptome after 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 | 4 weeks |
Outcome Measure Data
| Analysis Population Description |
|---|
| The data were analyzed combining results from two studies (33 from this study and additional 24 individuals from study NCT02234427; 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 | Participants treated with aspirin - there is no control group. Participant's baseline will act as their control. Aspirin: 81 mg daily for 4 weeks |
| Measure Participants | 57 |
| Mean (Standard Error) [FPKM difference for HBG1 Gene] |
77.1
(19.8)
|
Adverse Events
| Time Frame | ||
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Aspirin | |
| Arm/Group Description | Participants treated with aspirin - there is no control group. Participant's baseline will act as their control. Aspirin: 81 mg daily for 4 weeks | |
All Cause Mortality |
||
| Aspirin | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| Aspirin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/33 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Aspirin | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/33 (0%) | |
Limitations/Caveats
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.
Results Point of Contact
| Name/Title | Rehan Qayyum |
|---|---|
| Organization | Johns Hopkins School of Medicine |
| Phone | 410-955-7781 |
| rqayyum@jhmi.edu |
- K23HL105897-PARes-II
- K23HL105897