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

This study has been completed.
Sponsor:
Collaborators:
Netherlands Heart Foundation
Unilever R&D
Information provided by:
Wageningen University
ClinicalTrials.gov Identifier:
NCT00127452
First received: August 3, 2005
Last updated: July 6, 2010
Last verified: July 2010
  Purpose

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.

Condition Intervention
Cardiovascular Diseases
Dietary Supplement: margarine spread

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

Resource links provided by NLM:


Further study details as provided by Wageningen University:

Primary Outcome Measures:
  • 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) [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incident CVD, which comprises fatal CVD, non-fatal myocardial infarction, non-fatal cardiac arrest and non-fatal stroke [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]
  • Fatal CVD, which comprises mortality from ischaemic heart disease, fatal cardiac arrest, sudden death undefined, mortality from heart failure and fatal stroke [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]
  • Fatal CHD, which comprises mortality from ischaemic heart disease, mortality from cardiac arrest, and sudden death undefined [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]
  • All-causes mortality [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]
  • The composite of sudden death undefined and nonfatal and fatal cardiac arrest [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]
  • The composite of sudden death undefined, nonfatal and fatal cardiac arrest, and self-reported placement of any implantable cardioverter-defibrillator, verified in medical records [ Time Frame: monitored during intervention ] [ Designated as safety issue: No ]

Enrollment: 4837
Study Start Date: April 2002
Study Completion Date: June 2010
Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: EPA + DHA
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
Daily use of margarine spread (approximately 20 grams) during 40 months
Experimental: ALA
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
Daily use of margarine spread (approximately 20 grams) during 40 months
Experimental: EPA + DHA plus ALA
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
Daily use of margarine spread (approximately 20 grams) during 40 months
Placebo Comparator: Placebo
Margarine spread that contains no EPA, DHA or ALA (exchanged for oleic acid)
Dietary Supplement: margarine spread
Daily use of margarine spread (approximately 20 grams) during 40 months

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.

  Eligibility

Ages Eligible for Study:   60 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00127452

Locations
Netherlands
Medisch Centrum Alkmaar
Alkmaar, Netherlands, 1815 JD
Flevo Ziekenhuis
Almere, Netherlands, 1315 RA
Meander Medisch Centrum
Amersfoort, Netherlands, 3800 BM
Slotervaartziekenhuis
Amsterdam, Netherlands, 1066 EC
BovenIJ Ziekenhuis
Amsterdam, Netherlands, 1034 CS
Sint Lucas Andreas Ziekenhuis
Amsterdam, Netherlands, 1006 AE
Gelre ziekenhuizen
Apeldoorn, Netherlands
Lievensberg Ziekenhuis
Bergen op Zoom, Netherlands, 4600 AC
Rode Kruis Ziekenhuis
Beverwijk, Netherlands, 1940 EB
IJsselland Ziekenhuis
Capelle aan den IJssel, Netherlands
Ziekenhuis Gelderse Vallei
Ede, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands, 5623 EJ
Medisch Spectrum Twente
Enschede, Netherlands, 7500 AN
St. Anna Ziekenhuis
Geldrop, Netherlands
Oosterscheldeziekenhuis
Goes, Netherlands, 4462 RA
Ziekenhuis Hilversum
Hilversum, Netherlands, 1213 XZ
Diaconessenhuis
Leiden, Netherlands
Rijnland Ziekenhuis
Leiderdorp, Netherlands, 2353 GA
Sint Antonius Ziekenhuis
Nieuwegein, Netherlands, 3430 EM
Canisius Wilhelmina Ziekenhuis
Nijmegen, Netherlands
Havenziekenhuis
Rotterdam, Netherlands
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Haga Ziekenhuis, location Leyweg
The Hague, Netherlands, 2545 CH
Bronovo Ziekenhuis
The Hague, Netherlands, 2597 AX
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, 6700 EV
Zaans Medisch Centrum
Zaandam, Netherlands, 1502 DV
't Lange Land ziekenhuis
Zoetermeer, Netherlands
Isala Klinieken
Zwolle, Netherlands, 8011 JW
Sponsors and Collaborators
Wageningen University
Netherlands Heart Foundation
Unilever R&D
Investigators
Principal Investigator: Daan Kromhout, PhD MPH Wageningen University, The Netherlands
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Daan Kromhout, Wageningen University
ClinicalTrials.gov Identifier: NCT00127452     History of Changes
Obsolete Identifiers: NCT00139464
Other Study ID Numbers: METC-ZWH 0552, NHF-2000T401, L01.049, 5R01HL076200
Study First Received: August 3, 2005
Last Updated: July 6, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Wageningen University:
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

Additional relevant MeSH terms:
Cardiovascular Diseases
Myocardial Infarction
Myocardial Ischemia
Heart Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on September 16, 2014