Validation of an Assay to Measure Cyclooxygenase-1 Activity

Study Overview
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Brief Summary
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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
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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.

Official Title
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Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans

Conditions
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Healthy

Intervention / Treatment
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* Other: Chewable aspirin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Chewable aspirin<br>81 mg daily for 2 weeks | Other: Chewable aspirin<br>* chewable aspirin 81mg daily for 2 weeks<br>* Other names: acetylsalicylic acid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Thromboxane | SerumTxB2: They are formed from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects. | Baseline and at 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aspirin, cyclooxygenase-1, aspirin resistance, aspirin nonresponse, platelet, Normal volunteers