Healthy
Conditions
Keywords
aspirin, cyclooxygenase-1, aspirin resistance, aspirin nonresponse, platelet, Normal volunteers
Brief summary
The purpose of this study is to obtain a reference range for a newly developed assay of ex vivo platelet COX-1 activity in normal volunteers taking a routine clinical dose of aspirin.
Detailed description
Aspirin has been shown to reduce cardiovascular events in at-risk individuals, but some aspirin-treated patients fail to exhibit expected changes in bleeding time and platelet aggregation. Recent evidence has correlated aspirin non-response to poor cardiovascular outcomes. In order to study the mechanisms of aspirin resistance, an assay is needed to measure the catalytic activity of platelet cyclooxygenase (which should be inhibited by aspirin). A common assay in general use is the measurement of thromboxane B2 production in clotting whole blood. This measure, however, is influenced by genetic and environmental variations in the glass-activated coagulation pathway, albumin binding capacity, platelet activation pathways, arachidonic acid pools, and phospholipase activity. Our laboratory has developed a direct assay of platelet cyclooxygenase (COX-1) activity that is not influenced by these variations. This study will generate a reference range in normal volunteers taking a routine clinical dose of aspirin (81mg daily) for this assay.
Interventions
OTHERChewable aspirin
chewable aspirin 81mg daily for 2 weeks
Sponsors
Vanderbilt University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Non-smoker * No chronic medical illness * No chronic medications
Exclusion criteria
* Aspirin/NSAID use in preceding 14 days * History of chronic NSAID use * Currently taking NSAIDs, opioid analgesics, corticosteroids, or anticoagulants * History of coronary artery disease, myocardial infarction, coronary artery bypass grafting, percutaneous angioplasty, diabetes mellitus, or stroke. * History of hypertension * Body mass index \> 35 * History of gastric, duodenal, or esophageal ulcers or serious gastrointestinal bleed * History of frequent headaches, pain syndrome, or other condition requiring frequent use of analgesics * History of adverse reactions to aspirin * Screening platelet count \< 100,000/ul or \> 500,000/ul * Screening hematocrit \< 35% or \> 50% * Weight less than 110 pounds * Pregnant females
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks | 2 weeks | Determine the level of Thromboxane B2 at which patients with a result above are not fully inhibited, and patients with a TxB2 level below are fully inhibited. The reference range is the level of serum thromboxane at which participants below have fully inhibited COX-1 and participants above do not have fully inhibited COX-1 activity |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Thromboxane | Baseline and at 2 weeks | SerumTxB2: They are formed from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Chewable Aspirin 81 mg daily for 2 weeks
Chewable aspirin: chewable aspirin 81mg daily for 2 weeks | 54 |
| Total | 54 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 10 |
Baseline characteristics
| Characteristic | Chewable Aspirin |
|---|---|
| Age, Continuous | 33.5 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 38 Participants |
| Region of Enrollment United States | 54 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 64 |
| other Total, other adverse events | 0 / 64 |
| serious Total, serious adverse events | 0 / 64 |
Outcome results
Primary
A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks
Determine the level of Thromboxane B2 at which patients with a result above are not fully inhibited, and patients with a TxB2 level below are fully inhibited. The reference range is the level of serum thromboxane at which participants below have fully inhibited COX-1 and participants above do not have fully inhibited COX-1 activity
Time frame: 2 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Chewable Aspirin | A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks | 13 ng/ml |
Secondary
Serum Thromboxane
SerumTxB2: They are formed from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects.
Time frame: Baseline and at 2 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Chewable Aspirin | Serum Thromboxane | baseline | 284.2 ng/ml | Standard Error 11.53 |
| Chewable Aspirin | Serum Thromboxane | 2weeks | 9.542 ng/ml | Standard Error 0.92 |