Effects of Omacor and Aspirin on Platelet Function
Condition: Healthy
Study type: Interventional
Phase: Early Phase 1

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.
    

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.
    

Intervention name(s): Aspirin; omega-3 acid ethyl esters
Intervention type(s): Drug; Drug
Intervention description(s): generic aspirin; 4, 1 g capsules q.d.
Other intervention name(s): Omacor; Lovaza
Intervention MeSH terms: Aspirin
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: omega-3 fatty acids; aspirin; platelet aggregation; Healthy volunteers; no disease