The Effects of Omega-3 Fatty Acids on Aspirin Resistance

Increased Drug Resistance Clinical Trial

Official title:

The Effects of Omega-3 Fatty Acids on Aspirin Resistance

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00771914
• Other study ID #: Study Protocol 112421
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 14, 2008
• Last updated: October 31, 2012
• Start date: November 2008
• Est. completion date: January 2009

Study information

• Verified date: October 2012
• Source: University of Rochester
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: January 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 50 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Increased Drug Resistance

Intervention

Drug:
• Aspirin
Aspirin 81mg tablet
• Lovaza
Lovaza 4 grams
• Both Aspirin and Lovaza
Lovaza 4 grams plus aspirin 81 mg

Other:
• Placebo
Capsule resembling fish oil and a tablet resembling aspirin

Locations

Country	Name	City	State
United States	University of Rochester School of Medicine and Dentistry	Rochester	New York

Sponsors (4)

Lead Sponsor	Collaborator
University of Rochester	American College of Clinical Pharmacy, Cornell University, GlaxoSmithKline

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the Difference Between the Time to Clot Formation in Seconds at Baseline and After Each Treatment	The PFA-100 test measures platelet function as the time that it takes for a clot to form in a collagen-lined cartridge.	4 hours	No