Effects of Omacor and Aspirin on Platelet Function

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ClinicalTrials.gov Identifier: NCT00688961

Recruitment Status : Completed

First Posted : June 3, 2008

Last Update Posted : June 3, 2008

Sponsor:

Information provided by:

Sanford Research

Study Description

Brief Summary:

Omacor (now Lovaza) is a pharmaceutical omega-3 fatty acid product. Omega-3 fatty acids can affect blood clotting by altering the function of the blood platelets. Aspirin can do the same. The purpose of this study is to determine the individual and combined effects of these two agents on platelet function using a whole blood method.

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: Aspirin Drug: omega-3 acid ethyl esters	Early Phase 1

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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 Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	10 participants
Allocation:	Non-Randomized
Intervention Model:	Factorial Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Pilot Study of the Effects of Omacor (Alone and With Aspirin) on Platelet Function in Healthy Subjects
Study Start Date :	June 2007
Actual Primary Completion Date :	August 2007
Actual Study Completion Date :	August 2007

Resource links provided by the National Library of Medicine

Drug Information available for: Aspirin Omega-3-acid ethyl esters Lovaza

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
No Intervention: 1 Baseline
Experimental: 2 Aspirin (1 day after a single, 625 mg dose)	Drug: Aspirin generic aspirin
Experimental: 3 Omacor	Drug: omega-3 acid ethyl esters 4, 1 g capsules q.d. Other Names: Omacor Lovaza
Experimental: 4 Omacor plus aspirin	Drug: Aspirin generic aspirin Drug: omega-3 acid ethyl esters 4, 1 g capsules q.d. Other Names: Omacor Lovaza

Outcome Measures

Primary Outcome Measures :

Whole blood aggregometry in response to 4 agonists [ Time Frame: Day 1, 2, 29, and 30 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	21 Years to 60 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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.

Contacts and Locations

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 ClinicalTrials.gov identifier (NCT number): NCT00688961

Locations

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United States, South Dakota
Sanford Research/USD
Sioux Falls, South Dakota, United States, 57105

Sponsors and Collaborators

Sanford Research

More Information

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Responsible Party:	William S. Harris, Sanford Research/USD
ClinicalTrials.gov Identifier:	NCT00688961
Other Study ID Numbers:	WSH-001
First Posted:	June 3, 2008 Key Record Dates
Last Update Posted:	June 3, 2008
Last Verified:	May 2008

Keywords provided by Sanford Research:


omega-3 fatty acids aspirin platelet aggregation Healthy volunteers; no disease

Additional relevant MeSH terms:

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Aspirin Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics 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 Antipyretics

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