Validation of an Assay to Measure Cyclooxygenase-1 Activity

• Sponsor: Vanderbilt University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00761891
• Collaborator: (none)
• Enrollment: 64
• Location: 1
• Arm: 1
• Duration (Months): 32.1
• Patients Per Site Per Month: 2

Study Details

Study Description

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	Other: Chewable aspirin	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Validation of an Ex Vivo Cyclooxygenase-1 Catalytic Assay in Humans
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: May 1, 2008
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks [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

Secondary Outcome Measures

1. Serum Thromboxane [Baseline and at 2 weeks]

   SerumTxB2: They are formed from the prostaglandin endoperoxides and cause platelet aggregation, contraction of arteries, and other biological effects.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Vanderbilt University	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

• Vanderbilt University

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: John Oates, Professor of Medicine and Pharmacology, Vanderbilt University
• ClinicalTrials.gov Identifier: NCT00761891
• Other Study ID Numbers: 061190
• First Posted: Sep 30, 2008
• Last Update Posted: Apr 18, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by John Oates, Professor of Medicine and Pharmacology, Vanderbilt University: aspirin; cyclooxygenase-1; aspirin resistance; aspirin nonresponse; platelet; Normal volunteers
• Additional relevant MeSH terms: Aspirin

Study Results

Participant Flow

Arm/Group Title	Chewable Aspirin
Arm/Group Description	81 mg daily for 2 weeks Chewable aspirin: chewable aspirin 81mg daily for 2 weeks
Period Title: Overall Study
STARTED	64
COMPLETED	54
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Chewable Aspirin
Arm/Group Description	81 mg daily for 2 weeks Chewable aspirin: chewable aspirin 81mg daily for 2 weeks
Overall Participants	54
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	33.5
Sex: Female, Male (Count of Participants)
Female	28 51.9%
Male	26 48.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	5 9.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	9 16.7%
White	38 70.4%
More than one race	0 0%
Unknown or Not Reported	2 3.7%
Region of Enrollment (participants) [Number]
United States	54 100%

Outcome Measures

1. Primary Outcome

Title	A Reference Range in Normal Volunteers Taking a Routine Clinical Dose of Aspirin (81mg Daily) for 2 Weeks
Description	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
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chewable Aspirin
Arm/Group Description	81 mg daily for 2 weeks
Measure Participants	54
Number (75% Confidence Interval) [ng/ml]	13

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Chewable Aspirin
Arm/Group Description	81mg aspirin daily for 2 weeks
Measure Participants	54
baseline	284.2 (11.53)
2weeks	9.542 (0.92)

Adverse Events

Arm/Group Title	Enteric-coated Aspirin
Arm/Group Description	81 mg daily for 2 weeks Enteric-coated aspirin: enteric-coated aspirin 81mg daily for 2 weeks
All Cause Mortality
	Enteric-coated Aspirin
	Affected / at Risk (%)	# Events
Total	0/64 (0%)
Serious Adverse Events
	Enteric-coated Aspirin
	Affected / at Risk (%)	# Events
Total	0/64 (0%)
Other (Not Including Serious) Adverse Events
	Enteric-coated Aspirin
	Affected / at Risk (%)	# Events
Total	0/64 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.