Effects of Omacor and Aspirin on Platelet Function
A Pilot Study of the Effects of Omacor (Alone and With Aspirin) on Platelet Function in Healthy Subjects
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Overview
This study will explore the effects of 4 g/d of Omacor in healthy volunteers both with and without concomitant aspirin therapy. The study will utilize three different analytical approaches to assess platelet activation and function.
Objective
The purpose of this exploratory study is to gather preliminary information on the effects of Omacor on a platelet function in healthy volunteers, both with and without concomitant aspirin therapy, in order to lay the groundwork for future studies in cardiac patients taking Omacor in combination with aspirin and clopidogrel.
Background/Significance
Omacor (omega-3 fatty acid ethyl esters) is approved for treatment of severe hypertriglyceridemia, and may soon be approved for the treatment of moderate hypertriglyceridemia in combination with statins. In other words, the use of Omacor will continue to expand. The package insert notes that physicians should be attuned to the possibility of increased bleeding tendencies with high dose (4 g/d) Omacor use despite the fact that clinically significant bleeding has virtually never been reported with this dose (or even up to 7 g of EPA+DHA) in studies in patients on concomitant anti-platelet therapy undergoing highly invasive vascular procedures (e.g., diagnostic catheterization, angioplasty, coronary artery bypass grafting). Nevertheless, because omega-3 fatty acids are known to inhibit platelet function and to increase bleeding times(1), it is prudent to explore and carefully define the effects of this dose of Omacor on platelet composition and function.
Primary and Secondary Endpoints
The primary endpoint will be the effects of Omacor ± aspirin on platelet aggregation measured by whole blood impedence aggregometry in Harris's laboratory.
The secondary aims are to explore some of the molecular mechanisms by which omega-3 fatty acids and/or aspirin may alter platelet function. These include spreading assays, and tests of calcium and ATP release (described below). Even if the whole blood aggregation assays are not altered by Omacor treatment (they will be altered by aspirin treatment), these tests are sensitive to more subtle alterations in platelet function that could be missed in platelet aggregation assays. Alternatively, omega-3 FAs could impact two independent pathways in opposite directions, resulting in a cancelling out of the overall effect on platelet aggregation. These more focused experiments will be conducted at Dr. Mark Larson's laboratory at Augustana College.
Experimental Design and Methodology
Design This will be an open-label, pre- and post, 4-week trial. Blood will be drawn on day 1 (baseline), day 2 (1 day after taking 650 mg of aspirin), day 29 (after taking Omacor for 28 days), and day 30 (Omacor + 650 mg of aspirin). Platelet aggregation will be tested in each blood sample.
Subjects Ten healthy volunteers will be recruited from among the staff of Sanford Research/USD, Sanford School of Medicine, and Sanford Hospital; patients, students, visitors, and subordinates of the investigators will not be eligible. Subjects may be male or female and between the ages of 21 and 60, non-smokers, and taking no medications, vitamin pills, nutritional supplements or herbal preparations. Subjects may not have a history of allergic reactions to aspirin, fish or fish oils. Birth control pills are not allowed. Subject cannot have an allergy to aspirin or to non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, others), naproxen (Aleve, Naprosyn, Anaprox, others), indomethacin (Indocin), or ketoprofen (Orudis KT, Orudis, Oruvail), nabumetone (Relafen), oxaprozin (Daypro), or tartrazine. Other exclusions include: drinking more than three alcoholic beverages a day, or having any of the following conditions: an ulcer or bleeding in the stomach, liver or kidney disease, bleeding or blood clotting disorder (e.g., hemophilia), congestive heart failure, fluid retention, heart disease, high blood pressure, gout, asthma, arthritis, or nasal polyps.
Laboratory Methods Blood will be drawn into sodium citrate for all tests. Three agonists will be used in the whole blood aggregometry tests: thrombin, collagen and ADP(3). The output of this instrument (Chronolog Whole Blood Aggregometer, model 504) is in ohms, with higher impedance values indicating greater platelet aggregation. Because this test is conducted in whole blood (i.e., erythrocytes present), it is thought to be the most physiologically-relevant method for testing platelet function.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
South Dakota
-
Sioux Falls, South Dakota, United States, 57105
- Sanford Research/USD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects may be male or female and between the ages of 21 and 60,
- Non-smokers,
- Taking no medications, vitamin pills, nutritional supplements or herbal preparations.
Exclusion Criteria:
- Subjects may not have a history of allergic reactions to aspirin, fish or fish oils.
- Birth control pills are not allowed.
- Subject cannot have an allergy to aspirin or to non-steroidal anti-inflammatory drug (NSAID) such as ibuprofen (Motrin, Advil, others), naproxen (Aleve, Naprosyn, Anaprox, others), indomethacin (Indocin), or ketoprofen (Orudis KT, Orudis, Oruvail), nabumetone (Relafen), oxaprozin (Daypro), or tartrazine.
- Drinking more than three alcoholic beverages a day
Having any of the following conditions:
- an ulcer or bleeding in the stomach,
- liver or kidney disease,
- bleeding or blood clotting disorder (e.g., hemophilia),
- congestive heart failure,
- fluid retention,
- heart disease,
- high blood pressure,
- gout,
- asthma,
- arthritis, or
- nasal polyps.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Factorial Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
|
No Intervention: 1
Baseline
|
|
|
Experimental: 2
Aspirin (1 day after a single, 625 mg dose)
|
generic aspirin
|
|
Experimental: 3
Omacor
|
4, 1 g capsules q.d.
Other Names:
|
|
Experimental: 4
Omacor plus aspirin
|
generic aspirin
4, 1 g capsules q.d.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
|---|---|
|
Whole blood aggregometry in response to 4 agonists
Time Frame: Day 1, 2, 29, and 30
|
Day 1, 2, 29, and 30
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
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
- WSH-001
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