The Effects of Omega-3 Fatty Acids on Aspirin Resistance

Study Description

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Brief Summary:

The purpose of this study is to determine if omega-3 fatty acids enhance the antiplatelet effects of aspirin.

Condition or disease	Intervention/treatment	Phase
Increased Drug Resistance	Drug: Aspirin; Drug: Lovaza; Drug: Both Aspirin and Lovaza; Other: Placebo	Phase 1; Phase 2

Detailed Description:

Although aspirin has been a stalwart treatment in the prevention and treatment of myocardial infarction and stroke, it does not have its expected effects in a significant proportion of the population. This phenomenon has been termed "aspirin resistance". Omega-3 fatty acid supplementation has been associated with a reduced risk of sudden cardiac death and myocardial infarction. The beneficial effects of omega-3s are considered to be partially due to their ability to prevent platelet aggregation. However, the ability of omega-3s to enhance the effects of aspirin in those who suffer from aspirin resistance has not been determined. It is known that aspirin stimulates the production of potent lipid mediators from omega-3 fatty acids and that these mediators have powerful antiinflammatory and tissue-protective effects. Thus, the treatment of individuals at high risk for myocardial infarction and stroke with both aspirin and a pharmaceutical-grade omega-3 fatty acid medication may be a powerful combination in the prevention and treatment of life-threatening cardiovascular disease.

Study Protocol: Non-smoking male and female subjects between the ages of 18 and 50 not taking any medications, vitamin pills, nutritional supplements, or herbal preparations were recruited. Subjects with a history of chronic diseases (e.g. cardiovascular, renal, hepatic, neurodegenerative, neoplastic, metabolic {diabetes}, hypertension; based on screening medical history, a complete blood count, and comprehensive metabolic profile), or allergic reactions to aspirin, fish, fish oils, or non-steroidal anti-inflammatory drugs were excluded. Other exclusions included 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, high blood pressure, gout, asthma, arthritis, or nasal polyps. This was a randomized, placebo-controlled, double-blinded trial with a cross-over design. Each subject served as his/her own control. The study involved four visits four weeks apart, all hosted in the University of Rochester Clinical Research Center. At each separate study visit, each subject received (using a randomized protocol) placebo, 81 mg aspirin, 4 g Lovaza(R)(3.4g of EPA+DHA), or both aspirin and Lovaza(R). Thus, each subject received each of these treatments individually in a random fashion over the four visits. Subjects, Center staff, and investigators were blinded as to which treatment was given at each visit and this ensured by the study pharmacist making the tablets and capsules for each treatment appear identical. Prior to each visit, subjects ate a standard low-fat dinner the prior evening, then fasted for at least 8 hours prior to arrival at the Center. Subjects were required to abstain from taking aspirin or non-steroidal anti-inflammatory drugs for 10 days prior to each visit and omega-3 fatty acids for 30 days prior to the baseline study visit, and all subsequent clinic visits. Visits lasted approximately 6 hours, with subjects at bedrest. A venous catheter was placed in a peripheral vein (saline lock, 18 gauge or larger, {no heparin used} in the forearm) with blood drawn, at baseline and 4 hours post-treatment, into citrated tubes at each visit for Platelet Function Analyzer-100 (PFA-100-Siemens, Deerfield, IL) closure time testing. Subjects were provided with a standard low-fat breakfast after the baseline phlebotomy.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	27 participants
Allocation:	Randomized
Intervention Model:	Crossover Assignment
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:	Treatment
Official Title:	The Effects of Omega-3 Fatty Acids on Aspirin Resistance
Study Start Date :	November 2008
Actual Primary Completion Date :	January 2009
Actual Study Completion Date :	January 2009

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Placebo, Lovaza, Aspirin, Both Aspirin and Lovaza; First Placebo, then 4 grams of Lovaza, then 81mg of Aspirin, then both 4 grams of Lovaza and 81 mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet Drug: Lovaza; Lovaza 4 grams; Other Name: ethyl EPA + DHA; fish oil Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Name: Lovaza and aspirin Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Aspirin, Lovaza, Both Aspirin and Lovaza, Placebo; First 81mg of Aspirin, then 4 grams of Lovaza, then both 81mg of Aspirin and 4 grams of Lovaza, then placebo	Drug: Aspirin; Aspirin 81mg tablet Drug: Lovaza; Lovaza 4 grams; Other Name: ethyl EPA + DHA; fish oil Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Name: Lovaza and aspirin Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Lovaza, Both Aspirin and Lovaza, Placebo, Aspirin; First 4 grams of Lovaza, then both 81mg of Aspirin and 4 grams of Lovaza, then placebo, then 81mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet Drug: Lovaza; Lovaza 4 grams; Other Name: ethyl EPA + DHA; fish oil Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Name: Lovaza and aspirin Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin
Experimental: Both Aspirin and Lovaza, Placebo, Lovaza, Aspirin; First both 81mg of Aspirin and 4 grams of Lovaza, then placebo, then 4 grams of Lovaza, then 81mg of Aspirin	Drug: Aspirin; Aspirin 81mg tablet Drug: Lovaza; Lovaza 4 grams; Other Name: ethyl EPA + DHA; fish oil Drug: Both Aspirin and Lovaza; Lovaza 4 grams plus aspirin 81 mg; Other Name: Lovaza and aspirin Other: Placebo; Capsule resembling fish oil and a tablet resembling aspirin

Outcome Measures

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Primary Outcome Measures :

1. the Difference Between the Time to Clot Formation in Seconds at Baseline and After Each Treatment [ Time Frame: 4 hours ]
   The PFA-100 test measures platelet function as the time that it takes for a clot to form in a collagen-lined cartridge.

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 50 Years (Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

• Willing to participate by providing informed consent and committing to complete the study. This includes adhering to the study diet.
• No chronic disease by history and based on a complete blood count and comprehensive metabolic profile.
• Commitment to not taking aspirin, non-steroidal anti-inflammatory medications, and to limit fish intake to ≤2 meals during the 7 days prior to each CRC study period. They will also need to abstain from taking a list of over-the-counter medications that include aspirin. For the duration of the study, they will also be asked to abstain from taking fish and flax seed oil supplements.

Exclusion Criteria:

• Reports the presence of chronic disease (e.g. cardiovascular, renal, hepatic, neurodegenerative, neoplastic, metabolic {diabetes}, hypertension).
• Reports taking a systemic medication chronically.
• History of serious adverse reaction or allergy to aspirin or fish oil.
• Baseline platelet count <100 000 or >500 000, hematocrit <30%, or white blood cell count >20 000.
• Any abnormality from a screening CBC and complete blood count that suggests acute or chronic disease.
• Nicotine user.
• History of alcohol abuse
• Pregnancy by history or urine/serum pregnancy test
• History of intestinal malabsorption syndrome including gastric bypass surgery

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, New York
University of Rochester School of Medicine and Dentistry
Rochester, New York, United States, 14642

Sponsors and Collaborators

University of Rochester

GlaxoSmithKline

American College of Clinical Pharmacy

Cornell University

Investigators

Principal Investigator:	Robert C Block, MD, MPH	University of Rochester School of Medicine and Dentistry

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Robert Block, Principal Investigator, University of Rochester
ClinicalTrials.gov Identifier:	NCT00771914 History of Changes
Other Study ID Numbers:	Study Protocol 112421
First Posted:	October 15, 2008
Results First Posted:	June 29, 2012
Last Update Posted:	November 6, 2012
Last Verified:	October 2012

Keywords provided by Robert Block, University of Rochester:

aspirin; omega 3 fatty acids; Lovaza	myocardial infarction; aspirin resistance; cardiovascular disease

Additional relevant MeSH terms:

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