Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Vanderbilt University
- Enrollment
- 64
- Locations
- 1
- Primary Endpoint
- A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Other
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Chewable aspirin
81 mg daily for 2 weeks
Intervention: Chewable aspirin (Other)
Outcomes
Primary Outcomes
A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks
Time Frame: 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 Outcomes
- Serum Thromboxane(Baseline and at 2 weeks)
Investigators
John Oates
Professor of Medicine and Pharmacology
Vanderbilt University