Validation of an Assay to Measure Cyclooxygenase-1 Activity

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00761891
Recruitment Status : Completed
First Posted : September 30, 2008
Last Update Posted : December 7, 2015
Information provided by (Responsible Party):
John Oates, Vanderbilt University

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.

Condition or disease Intervention/treatment Phase
Healthy Drug: Enteric-coated aspirin Drug: Chewable aspirin Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Investigator)
Official Title: Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans
Study Start Date : May 2007
Actual Primary Completion Date : May 2008
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin
U.S. FDA Resources

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. d8-thromboxane B2 generated in ex vivo platelet COX-1 catalytic assay [ Time Frame: Baseline and after 2 weeks of aspirin ]
    measure d8-thromboxane B2

Secondary Outcome Measures :
  1. Platelet aggregation by optical aggregometry [ Time Frame: Baseline and after 2 weeks of aspirin ]
    Measure platelet aggregation

  2. Serum thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ]
    Measure serum thromboxane B2

  3. Urinary 11-dehydro-thromboxane B2 [ Time Frame: Baseline and after 2 weeks of aspirin ]
    Measure Urinary 11-dehydro-thromboxane B2

  4. Urinary prostacyclin metabolite [ Time Frame: Baseline and after 2 weeks of aspirin ]
    Measure Urinary prostacyclin metabolite

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00761891

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

Responsible Party: John Oates, Professor of Medicine and Pharmacology, Vanderbilt University Identifier: NCT00761891     History of Changes
Other Study ID Numbers: 061190
First Posted: September 30, 2008    Key Record Dates
Last Update Posted: December 7, 2015
Last Verified: December 2015

Keywords provided by John Oates, Vanderbilt University:
aspirin resistance
aspirin nonresponse
Normal volunteers

Additional relevant MeSH terms:
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors