Validation of an Assay to Measure Cyclooxygenase-1 Activity

Vanderbilt University64 enrolled

Overview

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.

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 Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

Chewable aspirinOTHER

chewable aspirin 81mg daily for 2 weeks

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Vanderbilt University

Nashville, Tennessee, United States

Outcomes

Primary Outcomes

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

Secondary Outcomes

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

Data from ClinicalTrials.gov

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