Validation of an Assay to Measure Cyclooxygenase-1 Activity - Full Text View

Sponsored by:	Vanderbilt University
Information provided by:	Vanderbilt University
ClinicalTrials.gov Identifier:	NCT00761891

Purpose

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.

Condition	Intervention
Healthy	Drug: aspirin

Drug Information available for: Acetylsalicylic acid

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Randomized, Single Blind (Investigator), Active Control, Parallel Assignment, Pharmacodynamics Study
Official Title:	Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans

Further study details as provided by Vanderbilt University:

Primary Outcome Measures:

d8-thromboxane B2 generated in ex vivo platelet COX-1 catalytic assay [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Platelet aggregation by optical aggregometry [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
Serum thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
Urinary 11-dehydro-thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
Urinary prostacyclin metabolite [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]

Enrollment:	60
Study Start Date:	May 2007
Study Completion Date:	May 2008
Primary Completion Date:	May 2008 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental	Drug: aspirin enteric-coated aspirin 81mg daily for 2 weeks
2: Active Comparator	Drug: aspirin chewable aspirin 81mg daily for 2 weeks

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. In addition, by using two aspirin formulations (enteric-coated and chewable), the study design additionally allows the secondary comparison of the effects of these two formulations on COX-1 inhibition.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00761891

Locations

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232

Sponsors and Collaborators

Vanderbilt University

Investigators

Principal Investigator:

John A Oates, MD

Vanderbilt University

More Information

Responsible Party:	Vanderbilt University ( John A. Oates )
Study ID Numbers:	061190
Study First Received:	September 26, 2008
Last Updated:	December 2, 2008
ClinicalTrials.gov Identifier:	NCT00761891
Health Authority:	United States: Institutional Review Board

Keywords provided by Vanderbilt University:

aspirin
cyclooxygenase-1
aspirin resistance

aspirin nonresponse
platelet
Normal volunteers

Study placed in the following topic categories:

Aspirin
Healthy

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Cyclooxygenase Inhibitors
Hematologic Agents
Physiological Effects of Drugs
Enzyme Inhibitors
Fibrinolytic Agents
Cardiovascular Agents
Pharmacologic Actions
Fibrin Modulating Agents

Analgesics, Non-Narcotic
Sensory System Agents
Therapeutic Uses
Platelet Aggregation Inhibitors
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 14, 2009