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

Cardiovascular Diseases Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00127452
• Other study ID #: METC-ZWH 0552
• Secondary ID: NHF-2000T401L01.
• Status: Completed
• Phase: N/A
• First received: August 3, 2005
• Last updated: July 6, 2010
• Start date: April 2002
• Est. completion date: June 2010

Study information

• Verified date: July 2010
• Source: Wageningen University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00139464

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4837
• Est. completion date: June 2010
• Est. primary completion date: November 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years to 80 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Myocardial Infarction

Intervention

Dietary Supplement:
• margarine spread
Daily use of margarine spread (approximately 20 grams) during 40 months

Locations

Country	Name	City	State
Netherlands	Medisch Centrum Alkmaar	Alkmaar
Netherlands	Flevo Ziekenhuis	Almere
Netherlands	Meander Medisch Centrum	Amersfoort
Netherlands	BovenIJ Ziekenhuis	Amsterdam
Netherlands	Sint Lucas Andreas Ziekenhuis	Amsterdam
Netherlands	Slotervaartziekenhuis	Amsterdam
Netherlands	Gelre ziekenhuizen	Apeldoorn
Netherlands	Lievensberg Ziekenhuis	Bergen op Zoom
Netherlands	Rode Kruis Ziekenhuis	Beverwijk
Netherlands	IJsselland Ziekenhuis	Capelle aan den IJssel
Netherlands	Ziekenhuis Gelderse Vallei	Ede
Netherlands	Catharina Ziekenhuis	Eindhoven
Netherlands	Medisch Spectrum Twente	Enschede
Netherlands	St. Anna Ziekenhuis	Geldrop
Netherlands	Oosterscheldeziekenhuis	Goes
Netherlands	Ziekenhuis Hilversum	Hilversum
Netherlands	Diaconessenhuis	Leiden
Netherlands	Rijnland Ziekenhuis	Leiderdorp
Netherlands	Sint Antonius Ziekenhuis	Nieuwegein
Netherlands	Canisius Wilhelmina Ziekenhuis	Nijmegen
Netherlands	Erasmus MC	Rotterdam
Netherlands	Havenziekenhuis	Rotterdam
Netherlands	Bronovo Ziekenhuis	The Hague
Netherlands	Haga Ziekenhuis, location Leyweg	The Hague
Netherlands	Haga Ziekenhuis, location Sportlaan	The Hague
Netherlands	Twee Steden Ziekenhuis	Tilburg
Netherlands	Maxima Medisch Centrum	Veldhoven
Netherlands	Alysis Ziekenhuis	Velp
Netherlands	Wageningen University, Division of Human Nutrition	Wageningen
Netherlands	Zaans Medisch Centrum	Zaandam
Netherlands	't Lange Land ziekenhuis	Zoetermeer
Netherlands	Isala Klinieken	Zwolle

Sponsors (4)

Lead Sponsor	Collaborator
Wageningen University	National Heart, Lung, and Blood Institute (NHLBI), Netherlands Heart Foundation, Unilever R&D

Country where clinical trial is conducted

Netherlands, 

References & Publications (1)

Geleijnse JM, Giltay EJ, Schouten EG, de Goede J, Oude Griep LM, Teitsma-Jansen AM, Katan MB, Kromhout D; Alpha Omega Trial Group. Effect of low doses of n-3 fatty acids on cardiovascular diseases in 4,837 post-myocardial infarction patients: design and baseline characteristics of the Alpha Omega Trial. Am Heart J. 2010 Apr;159(4):539-546.e2. doi: 10.1016/j.ahj.2009.12.033. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Incident CVD, which comprises fatal CVD, non-fatal myocardial infarction, non-fatal cardiac arrest and non-fatal stroke		monitored during intervention	No
Secondary	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	No
Secondary	Fatal CHD, which comprises mortality from ischaemic heart disease, mortality from cardiac arrest, and sudden death undefined		monitored during intervention	No
Secondary	All-causes mortality		monitored during intervention	No
Secondary	The composite of sudden death undefined and nonfatal and fatal cardiac arrest		monitored during intervention	No
Secondary	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	No

External Links

•   Division of Human Nutrition, Wageningen University, The Netherlands
•   Information site of the Alpha Omega Trial; statistical analysis plans are posted here
•   Netherlands Heart Foundation
•   The Graduate School VLAG, Wageningen, The Netherlands
•   Wageningen University and Research Centre