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Alpha Omega Trial: Study of Omega-3 Fatty Acids and Coronary Mortality

Not Applicable
Completed
Conditions
Cardiovascular Diseases
Interventions
Dietary Supplement: margarine spread
Registration Number
NCT00127452
Lead Sponsor
Wageningen University
Brief 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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
4837
Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
EPA + DHAmargarine spreadMargarine spread that yields 400 mg of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) per day for average margarine use of 20 grams per day
ALAmargarine spreadMargarine spread that yields 2 grams of alpha-linolenic acid (ALA) per day for average margarine use of 20 grams per day
EPA + DHA plus ALAmargarine spreadMargarine spread that yields 400 mg of EPA + DHA per day plus 2 grams of ALA per day, for average margarine use of 20 grams per day
Placebomargarine spreadMargarine spread that contains no EPA, DHA or ALA (exchanged for oleic acid)
Primary Outcome Measures
NameTimeMethod
Major cardiovascular events, which comprises fatal cardiovascular diseases (CVD), non-fatal myocardial infarction, non-fatal cardiac arrest, non-fatal stroke and cardiac interventions (PCI and CABG)monitored during intervention
Secondary Outcome Measures
NameTimeMethod
Incident CVD, which comprises fatal CVD, non-fatal myocardial infarction, non-fatal cardiac arrest and non-fatal strokemonitored during intervention
Fatal CVD, which comprises mortality from ischaemic heart disease, fatal cardiac arrest, sudden death undefined, mortality from heart failure and fatal strokemonitored during intervention
Fatal CHD, which comprises mortality from ischaemic heart disease, mortality from cardiac arrest, and sudden death undefinedmonitored during intervention
All-causes mortalitymonitored during intervention
The composite of sudden death undefined and nonfatal and fatal cardiac arrestmonitored during intervention
The composite of sudden death undefined, nonfatal and fatal cardiac arrest, and self-reported placement of any implantable cardioverter-defibrillator, verified in medical recordsmonitored during intervention

Trial Locations

Locations (32)

Slotervaartziekenhuis

🇳🇱

Amsterdam, Netherlands

Ziekenhuis Gelderse Vallei

🇳🇱

Ede, Netherlands

Twee Steden Ziekenhuis

🇳🇱

Tilburg, Netherlands

Flevo Ziekenhuis

🇳🇱

Almere, Netherlands

Catharina Ziekenhuis

🇳🇱

Eindhoven, Netherlands

Wageningen University, Division of Human Nutrition

🇳🇱

Wageningen, Netherlands

't Lange Land ziekenhuis

🇳🇱

Zoetermeer, Netherlands

Isala Klinieken

🇳🇱

Zwolle, Netherlands

Gelre ziekenhuizen

🇳🇱

Apeldoorn, Netherlands

Maxima Medisch Centrum

🇳🇱

Veldhoven, Netherlands

Meander Medisch Centrum

🇳🇱

Amersfoort, Netherlands

Sint Lucas Andreas Ziekenhuis

🇳🇱

Amsterdam, Netherlands

Havenziekenhuis

🇳🇱

Rotterdam, Netherlands

Haga Ziekenhuis, location Sportlaan

🇳🇱

The Hague, Netherlands

BovenIJ Ziekenhuis

🇳🇱

Amsterdam, Netherlands

Diaconessenhuis

🇳🇱

Leiden, Netherlands

Bronovo Ziekenhuis

🇳🇱

The Hague, Netherlands

Medisch Centrum Alkmaar

🇳🇱

Alkmaar, Netherlands

Lievensberg Ziekenhuis

🇳🇱

Bergen op Zoom, Netherlands

Rode Kruis Ziekenhuis

🇳🇱

Beverwijk, Netherlands

IJsselland Ziekenhuis

🇳🇱

Capelle aan den IJssel, Netherlands

Medisch Spectrum Twente

🇳🇱

Enschede, Netherlands

St. Anna Ziekenhuis

🇳🇱

Geldrop, Netherlands

Oosterscheldeziekenhuis

🇳🇱

Goes, Netherlands

Ziekenhuis Hilversum

🇳🇱

Hilversum, Netherlands

Rijnland Ziekenhuis

🇳🇱

Leiderdorp, Netherlands

Zaans Medisch Centrum

🇳🇱

Zaandam, Netherlands

Sint Antonius Ziekenhuis

🇳🇱

Nieuwegein, Netherlands

Canisius Wilhelmina Ziekenhuis

🇳🇱

Nijmegen, Netherlands

Erasmus MC

🇳🇱

Rotterdam, Netherlands

Haga Ziekenhuis, location Leyweg

🇳🇱

The Hague, Netherlands

Alysis Ziekenhuis

🇳🇱

Velp, Netherlands

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