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Validation of an Assay to Measure Cyclooxygenase-1 Activity

This study has been completed.
Sponsor:
Information provided by:
Vanderbilt University
ClinicalTrials.gov Identifier:
NCT00761891
First received: September 26, 2008
Last updated: March 21, 2011
Last verified: March 2011
History of Changes
  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

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:

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

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: January 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: aspirin
enteric-coated aspirin 81mg daily for 2 weeks
Other Name: acetylsalicylic acid
Active Comparator: 2 Drug: 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.

  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

No publications provided

Responsible Party: John A. Oates, Vanderbilt University
ClinicalTrials.gov Identifier: NCT00761891     History of Changes
Other Study ID Numbers: 061190
Study First Received: September 26, 2008
Last Updated: March 21, 2011
Health Authority: United States: Institutional Review Board

Keywords provided by Vanderbilt University:
aspirin
cyclooxygenase-1
aspirin resistance
 aspirin nonresponse
platelet
Normal volunteers

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

ClinicalTrials.gov processed this record on May 21, 2013