Clinical trial NCT00761891: Validation of an Assay to Measure Cyclooxygenase-1 Activity
Official title: Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: aspirin
cyclooxygenase-1
aspirin resistance
aspirin nonresponse
platelet
Normal volunteers
Lead sponsor: Vanderbilt University Medical Center
Sponsor class: OTHER
First posted: 2008-09-30
Enrollment: 64
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

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.

Eligibility criteria: 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

Primary outcomes:
measure: A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks
timeFrame: 2 weeks
Secondary outcomes:
measure: Serum Thromboxane
timeFrame: Baseline and at 2 weeks
Other outcomes:
Locations:
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Vanderbilt University
name: John A Oates, MD
role: PRINCIPAL_INVESTIGATOR
References: