Validation of an Assay to Measure Cyclooxygenase-1 Activity

This study has been completed.
Information provided by (Responsible Party):
John Oates, Vanderbilt University Identifier:
First received: September 26, 2008
Last updated: December 4, 2015
Last verified: December 2015
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
Drug: Enteric-coated aspirin
Drug: Chewable aspirin

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Investigator)
Official Title: Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans

Resource links provided by NLM:

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 ]
    measure d8-thromboxane B2

Secondary Outcome Measures:
  • Platelet aggregation by optical aggregometry [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure platelet aggregation

  • Serum thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure serum thromboxane B2

  • Urinary 11-dehydro-thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure Urinary 11-dehydro-thromboxane B2

  • Urinary prostacyclin metabolite [ Time Frame: Baseline and after 2 weeks of aspirin ] [ Designated as safety issue: No ]
    Measure Urinary prostacyclin metabolite

Enrollment: 60
Study Start Date: May 2007
Study Completion Date: January 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Enteric-coated aspirin
81 mg daily for 2 weeks
Drug: Enteric-coated aspirin
enteric-coated aspirin 81mg daily for 2 weeks
Other Name: acetylsalicylic acid
Active Comparator: Chewable aspirin
81 mg daily for 2 weeks
Drug: Chewable aspirin
chewable aspirin 81mg daily for 2 weeks
Other Name: acetylsalicylic acid

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.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
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Please refer to this study by its identifier: NCT00761891

United States, Tennessee
Vanderbilt University
Nashville, Tennessee, United States, 37232
Sponsors and Collaborators
Vanderbilt University
Principal Investigator: John A Oates, MD Vanderbilt University
  More Information

No publications provided

Responsible Party: John Oates, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT00761891     History of Changes
Other Study ID Numbers: 061190 
Study First Received: September 26, 2008
Last Updated: December 4, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
aspirin resistance
aspirin nonresponse
Normal volunteers

Additional relevant MeSH terms:
Analgesics, Non-Narcotic
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antirheumatic Agents
Cardiovascular Agents
Central Nervous System Agents
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Platelet Aggregation Inhibitors
Sensory System Agents
Therapeutic Uses processed this record on February 08, 2016