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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Alpha Omega Trial: A Randomised, Placebo Controlled, Double Blind Intervention Study of the Effect of Low Doses of Omega-3 Fatty Acids on Cardiovascular Diseases in Patients With a History of Myocardial Infarction

Conditions
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Cardiovascular Diseases

Intervention / Treatment
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* Dietary Supplement: margarine spread


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Men and women Aged 60 through 80 y Verified clinically diagnosed myocardial infarction up to 10 y before randomization Written informed consent Exclusion criteria: Living in a nursing home or other institution Participation in another scientific study Habitual margarine intake < 10 g per day Habitual fish intake > 150 g per day Habitual alcohol intake > 6 drinks per day Use of fish oil capsules or other supplements containing omega-3 fatty acids Presence of cancer with < 1 y of life expectancy Cognitive impairment, as indicated by the Mini Mental State Examination (score <= 21) Unintended weight loss > 5 kg in the past year Lack of facilities for cooled margarine storage at home Inability or unwillingness to comply with study procedures

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: EPA + DHA<br>Margarine spread that yields 400 mg of eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA) per day for average margarine use of 20 grams per day | Dietary Supplement: margarine spread<br>* Daily use of margarine spread (approximately 20 grams) during 40 months<br>|
| Experimental: ALA<br>Margarine spread that yields 2 grams of alpha-linolenic acid (ALA) per day for average margarine use of 20 grams per day | Dietary Supplement: margarine spread<br>* Daily use of margarine spread (approximately 20 grams) during 40 months<br>|
| Experimental: EPA + DHA plus ALA<br>Margarine 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 | Dietary Supplement: margarine spread<br>* Daily use of margarine spread (approximately 20 grams) during 40 months<br>|
| Placebo Comparator: Placebo<br>Margarine spread that contains no EPA, DHA or ALA (exchanged for oleic acid) | Dietary Supplement: margarine spread<br>* Daily use of margarine spread (approximately 20 grams) during 40 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incident CVD, which comprises fatal CVD, non-fatal myocardial infarction, non-fatal cardiac arrest and non-fatal stroke |  | monitored during intervention | 
| Fatal CVD, which comprises mortality from ischaemic heart disease, fatal cardiac arrest, sudden death undefined, mortality from heart failure and fatal stroke |  | monitored during intervention | 
| Fatal CHD, which comprises mortality from ischaemic heart disease, mortality from cardiac arrest, and sudden death undefined |  | monitored during intervention | 
| All-causes mortality |  | monitored during intervention | 
| The composite of sudden death undefined and nonfatal and fatal cardiac arrest |  | monitored 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 records |  | monitored during intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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