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The aim of the study is to test whether genetic variation in the alpha 2A adrenergic receptor affects diurnal variation in platelet aggregation.
There is a marked diurnal fluctuation in the occurrence of acute myocardial infarction and sudden death, with peak incidences occurring in the early morning. Platelet aggregation has also been shown to increase in the early morning. The investigators will test the hypothesis that alpha 2a-adrenergic receptor (ADRA2A) genetic variation, specifically haplotype 4, affects platelet aggregation. The investigators will compare diurnal platelet aggregation in haplotype 4 subjects with subjects in the other haplotype families. In addition, the investigators will compare platelet aggregation after the cold pressor test in haplotype 4 with the other haplotype families. If there are no differences among haplotypes, then the haplotypes will be combined to analyze.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Healthy volunteers | Normal healthy volunteers |
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| Measure | Description | Time Frame |
|---|---|---|
| LogEC50 Platelet Aggregation | EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses. | at 6am and 930am |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation | Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. | at 6am and 930am |
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Inclusion Criteria:
Exclusion Criteria:
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Healthy subjects will be recruited by advertisement and word-of-mouth.
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| Name | Affiliation | Role |
|---|---|---|
| Michael Stein, MBChB | Vanderbilt University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| the Vanderbilt University General Clinical Research Center | Nashville | Tennessee | 37232 | United States |
all IDP that underlie results in a publication
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6 months after publication
Access Criteria:
IPD will be shared on request made to the PI. Criteria: Data is not to be shared. Data should only be used for biomedical research. Researchers requesting access will need appropriate IRB approval and sign a data use agreement.
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Healthy normotensive, non-smokers Caucasians and African-Americans aged 18-45 years were recruited via flyers and word of mouth from 2012-2015. No medications except oral contraceptives within two weeks and no antiplatelet medications within three weeks of the study. Women were studied in the first 14 days of their menstrual cycle.
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| ID | Title | Description |
|---|---|---|
| FG000 | Healthy Volunteers | Normal healthy volunteers |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Healthy Volunteers | Normal healthy volunteers |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | LogEC50 Platelet Aggregation | EC50 represents the epinephrine concentration that produced 50% of maximal platelet aggregation (representing sensitivity to epinephrine) EC50 values were not normally distributed and were log-transformed for analyses. | outcome data could not be collected on all subjects, since unable to draw enough blood at a particular timepoint | Posted | Mean | Standard Deviation | nM | at 6am and 930am |
|
|
Adverse event data was collected from the time participant was admitted to the Clinical Research Center the evening before the study, to the end of the study, a 24 hour period.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Healthy Volunteers | Normal healthy volunteers |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| acute right groin pain | General disorders | Non-systematic Assessment | Study volunteer experienced acute right groin pain. He was taken to the Emergency Department treated with painkillers--had normal X-ray and MRI showing normal appearance of hip. Discharged from ED on analgesics--ED diagnosis "acute right groin pain". |
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Healthy young subjects studied, thus findings may not apply to different populations. Plasma catecholamines are an indirect measure of sympathetic activity--norepinephrine spillover would be more precise, but is technically demanding, not feasible.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. C. M. Stein | Vanderbilt University Medical Center | 615-936-3420 | mike.stein@vanderbilt.edu |
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| ID | Term |
|---|---|
| D009203 | Myocardial Infarction |
| ID | Term |
|---|---|
| D017202 | Myocardial Ischemia |
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D014652 | Vascular Diseases |
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Blood samples for DNA and plasma/serum for subsequent biomarker analysis if required.
| Percentage, Collagen Induced Platelet Aggregation |
Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. |
| at 6am and 930am |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
|
|
| Secondary | Percentage, Adenosine Diphosphate (ADP) Induced Platelet Aggregation | Blood samples were taken from participants and centrifuged. Adenosine Diphosphate (ADP) at a fixed concentration of 2.5 uM was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. | some outcome data could not be collected for all subjects, unable to draw enough blood for a particular timepoint | Posted | Mean | Standard Deviation | percentage of aggregation | at 6am and 930am |
|
|
|
| Secondary | Percentage, Collagen Induced Platelet Aggregation | Blood samples were taken from participants and centrifuged. Collagen at a fixed concentration of 2.5 ug/ml was added. Agonist-induced platelet aggregation was expressed as the percentage aggregation after 6 minutes of stimulation. | Some outcome date could not be collected for all subjects, unable to draw enough blood at a particular time point. | Posted | Mean | Standard Deviation | percentage of platelet aggregation | at 6am and 930am |
|
|
|
| 1 |
| 117 |
| 0 |
| 117 |
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| D007238 |
| Infarction |
| D007511 | Ischemia |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009336 | Necrosis |