Validation of an Assay to Measure Cyclooxygenase-1 Activity

Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans

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.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Other: Chewable 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.

• Study Type: Interventional
• Enrollment (Actual): 64
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Chewable aspirin; 81 mg daily for 2 weeks	Other: Chewable aspirin; chewable aspirin 81mg daily for 2 weeks; Other Names: acetylsalicylic acid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks	Determine the level of Thromboxane B2 at which patients with a result above are not fully inhibited, and patients with a TxB2 level below are fully inhibited. The reference range is the level of serum thromboxane at which participants below have fully inhibited COX-1 and participants above do not have fully inhibited COX-1 activity	2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Thromboxane	SerumTxB2: They are formed from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects.	Baseline and at 2 weeks

Collaborators and Investigators

• Sponsor: Vanderbilt University
• Investigators: Principal Investigator: John A Oates, MD, Vanderbilt University

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): May 1, 2008
• Study Completion (Actual): January 1, 2010

Study Registration Dates

• First Submitted: September 26, 2008
• First Submitted That Met QC Criteria: September 29, 2008
• First Posted (Estimate): September 30, 2008

Study Record Updates

• Last Update Posted (Actual): April 18, 2019
• Last Update Submitted That Met QC Criteria: April 17, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: platelet; aspirin; aspirin resistance; cyclooxygenase-1; aspirin nonresponse; Normal volunteers
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Fibrinolytic Agents; Fibrin Modulating Agents; Platelet Aggregation Inhibitors; Cyclooxygenase Inhibitors; Antipyretics; Aspirin
• Other Study ID Numbers: 061190

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No