Alpha Omega Trial: Study of Omega-3 Fatty Acids and Coronary Mortality
Condition: Cardiovascular Diseases
MeSH terms: Cardiovascular Diseases
Study type: Interventional

Summary: 
      The Alpha Omega Trial is a randomized, placebo-controlled, double-blind dietary intervention
      study in 4837 postmyocardial infarction patients in the Netherlands to examine whether
      incidence of cardiovascular diseases during 40 months of follow-up can be prevented by low
      doses of omega-3 polyunsaturated fatty acids. The key objectives are:

        -  to examine the effect of low-dose supplementation (400 mg/day) of eicosapentaenoic acid
           and docosahexaenoic acid on incidence of cardiovascular diseases; and

        -  to examine the effect of low-dose supplementation (2 g/day) of alpha-linolenic acid on
           incidence of cardiovascular diseases.
    

Detailed description: 
      Whether dietary omega-3 (or n-3) polyunsaturated fatty acids are causally related to risk of
      cardiovascular diseases (CVD) is a major, unresolved question in preventive cardiology.
      Essential n-3 fatty acids are eicosapentaenoic acid (EPA; C20:5, n-3) and docosahexaenoic
      acid (DHA; C22:6, n-3) on one hand, and their parent compound alpha-linolenic acid (ALA;
      C18:3, n-3) on the other hand. The intake of n-3 fatty acids is below recommended levels in
      most Western populations. The Alpha Omega Trial is a randomized, double-blind,
      placebo-controlled study of the effect of low-dose supplementation of ALA and EPA-DHA on CVD.
      A total of 4837 Dutch men and women aged 60-80 years who had a myocardial infarction in the
      past 10 years are randomly allocated to 2 g/d of ALA, 400 mg/d of EPA-DHA, 2 g/d ALA + 400
      mg/d EPA-DHA, or placebo, for 40 months. Increased intake of n-3 fatty acids is achieved
      through daily use of 20 g of margarine on bread. Margarines for all treatment groups are
      similar in taste and appearance. The primary outcome of the trial is 'major cardiovascular
      events', which comprises incident CVD and cardiac interventions (PCI and CABG) during
      follow-up. Secondary endpoints are incident CVD, fatal CVD, fatal CHD and all-causes
      mortality. Complete follow-up for vital status is achieved. Cause-specific mortality is coded
      by an independent Endpoint Adjudication Committee. Physical examination, blood sampling and
      data collection on diet and lifestyle are performed in all subjects at baseline, in 810
      randomly selected subjects after 20 months of intervention, and in 58% of the cohort at the
      end of follow-up. Cardiovascular health, serious adverse events, lifestyle, fish intake and
      margarine use are monitored in all subjects by yearly telephone interviews. Compliance is
      continuously monitored by registration of margarine tubs. An objective biomarker of
      compliance (i.e. plasma n-3 fatty acids) is obtained in randomly selected subjects at
      baseline and after 20 and 40 months of intervention. The Alpha Omega Trial could provide a
      sound scientific basis for dietary recommendations on intake of ALA and EPA-DHA, in order to
      reduce the burden of cardiovascular diseases.
    

Intervention name(s): margarine spread
Intervention type(s): Dietary Supplement
Intervention description(s): Daily use of margarine spread (approximately 20 grams) during 40 months
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: alpha-linolenic acid; cardiovascular diseases; coronary heart disease; coronary patients; DHA; dietary intervention; dietary supplementation; docosahexaenoic acid; eicosapentaenoic acid; EPA; fish oil; fish fatty acids; human subjects; ischaemic heart disease; margarine; marine fatty acids; mortality; myocardial infarction; n-3 fatty acids; n-3 polyunsaturated fatty acids; n-3 PUFA; omega-3 fatty acids; omega-3 polyunsaturated fatty acids; prevention; randomized controlled trial; secondary prevention