The Effects of Omega-3 Fatty Acids on Aspirin Resistance

This study has been completed.
Sponsor:
Collaborators:
GlaxoSmithKline
American College of Clinical Pharmacy
Cornell University
Information provided by (Responsible Party):
Robert Block, University of Rochester
ClinicalTrials.gov Identifier:
NCT00771914
First received: October 14, 2008
Last updated: October 31, 2012
Last verified: October 2012
  Purpose

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


Condition Intervention Phase
Increased Drug Resistance
Drug: Aspirin
Drug: Lovaza
Drug: Both Aspirin and Lovaza
Other: Placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Effects of Omega-3 Fatty Acids on Aspirin Resistance

Resource links provided by NLM:


Further study details as provided by University of Rochester:

Primary Outcome Measures:
  • the Difference Between the Time to Clot Formation in Seconds at Baseline and After Each Treatment [ Time Frame: 4 hours ] [ Designated as safety issue: No ]
    The PFA-100 test measures platelet function as the time that it takes for a clot to form in a collagen-lined cartridge.


Enrollment: 27
Study Start Date: November 2008
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Other Name: Placebo
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
Other Name: Placebo
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
Other Name: Placebo
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
Other Name: Placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00771914

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

No publications provided

Responsible Party: Robert Block, Principal Investigator, University of Rochester
ClinicalTrials.gov Identifier: NCT00771914     History of Changes
Other Study ID Numbers: Study Protocol 112421
Study First Received: October 14, 2008
Results First Received: October 10, 2011
Last Updated: October 31, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by 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
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Hematologic Agents
Platelet Aggregation Inhibitors
Cyclooxygenase Inhibitors
Enzyme Inhibitors
Antipyretics
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 21, 2014