Clinical trial NCT00127452: Alpha Omega Trial: Study of Omega-3 Fatty Acids and Coronary Mortality
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
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
Lead sponsor: Wageningen University
Sponsor class: OTHER
Collaborators: name: Netherlands Heart Foundation
name: National Heart, Lung, and Blood Institute (NHLBI)
name: Unilever R&D
First posted: 2005-08-05
Enrollment: 4837
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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

Primary outcomes:
measure: 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)
timeFrame: monitored during intervention
Secondary outcomes:
measure: Incident CVD, which comprises fatal CVD, non-fatal myocardial infarction, non-fatal cardiac arrest and non-fatal stroke
timeFrame: monitored during intervention
measure: Fatal CVD, which comprises mortality from ischaemic heart disease, fatal cardiac arrest, sudden death undefined, mortality from heart failure and fatal stroke
timeFrame: monitored during intervention
measure: Fatal CHD, which comprises mortality from ischaemic heart disease, mortality from cardiac arrest, and sudden death undefined
timeFrame: monitored during intervention
measure: All-causes mortality
timeFrame: monitored during intervention
measure: The composite of sudden death undefined and nonfatal and fatal cardiac arrest
timeFrame: monitored during intervention
measure: The composite of sudden death undefined, nonfatal and fatal cardiac arrest, and self-reported placement of any implantable cardioverter-defibrillator, verified in medical records
timeFrame: monitored during intervention
Other outcomes:
Locations:
city: Alkmaar
country: Netherlands
facility: Medisch Centrum Alkmaar
city: Almere
country: Netherlands
facility: Flevo Ziekenhuis
city: Amersfoort
country: Netherlands
facility: Meander Medisch Centrum
city: Amsterdam
country: Netherlands
facility: Sint Lucas Andreas Ziekenhuis
city: Amsterdam
country: Netherlands
facility: BovenIJ Ziekenhuis
city: Amsterdam
country: Netherlands
facility: Slotervaartziekenhuis
city: Apeldoorn
country: Netherlands
facility: Gelre ziekenhuizen
city: Bergen op Zoom
country: Netherlands
facility: Lievensberg Ziekenhuis
city: Beverwijk
country: Netherlands
facility: Rode Kruis Ziekenhuis
city: Capelle aan den IJssel
country: Netherlands
facility: IJsselland Ziekenhuis
city: Ede
country: Netherlands
facility: Ziekenhuis Gelderse Vallei
city: Eindhoven
country: Netherlands
facility: Catharina Ziekenhuis
city: Enschede
country: Netherlands
facility: Medisch Spectrum Twente
city: Geldrop
country: Netherlands
facility: St. Anna Ziekenhuis
city: Goes
country: Netherlands
facility: Oosterscheldeziekenhuis
city: Hilversum
country: Netherlands
facility: Ziekenhuis Hilversum
city: Leiden
country: Netherlands
facility: Diaconessenhuis
city: Leiderdorp
country: Netherlands
facility: Rijnland Ziekenhuis
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis
city: Nijmegen
country: Netherlands
facility: Canisius Wilhelmina Ziekenhuis
city: Rotterdam
country: Netherlands
facility: Erasmus MC
city: Rotterdam
country: Netherlands
facility: Havenziekenhuis
city: The Hague
country: Netherlands
facility: Haga Ziekenhuis, location Leyweg
city: The Hague
country: Netherlands
facility: Bronovo Ziekenhuis
city: The Hague
country: Netherlands
facility: Haga Ziekenhuis, location Sportlaan
city: Tilburg
country: Netherlands
facility: Twee Steden Ziekenhuis
city: Veldhoven
country: Netherlands
facility: Maxima Medisch Centrum
city: Velp
country: Netherlands
facility: Alysis Ziekenhuis
city: Wageningen
country: Netherlands
facility: Wageningen University, Division of Human Nutrition
city: Zaandam
country: Netherlands
facility: Zaans Medisch Centrum
city: Zoetermeer
country: Netherlands
facility: 't Lange Land ziekenhuis
city: Zwolle
country: Netherlands
facility: Isala Klinieken
Study officials:
affiliation: Wageningen University, The Netherlands
name: Daan Kromhout, PhD MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Pertiwi K, Wanders AJ, Harbers MC, Kupers LK, Soedamah-Muthu SS, de Goede J, Zock PL, Geleijnse JM. Plasma and Dietary Linoleic Acid and 3-Year Risk of Type 2 Diabetes After Myocardial Infarction: A Prospective Analysis in the Alpha Omega Cohort. Diabetes Care. 2020 Feb;43(2):358-365. doi: 10.2337/dc19-1483. Epub 2019 Nov 14.
citation: Sijtsma FP, Soedamah-Muthu SS, de Goede J, Oude Griep LM, Geleijnse JM, Giltay EJ, de Boer MJ, Jacobs DR Jr, Kromhout D. Healthy eating and lower mortality risk in a large cohort of cardiac patients who received state-of-the-art drug treatment. Am J Clin Nutr. 2015 Dec;102(6):1527-33. doi: 10.3945/ajcn.115.112276. Epub 2015 Oct 21.
citation: Hoogeveen EK, Geleijnse JM, Kromhout D, Stijnen T, Gemen EF, Kusters R, Giltay EJ. Effect of omega-3 fatty acids on kidney function after myocardial infarction: the Alpha Omega Trial. Clin J Am Soc Nephrol. 2014 Oct 7;9(10):1676-83. doi: 10.2215/CJN.10441013. Epub 2014 Aug 7.
citation: Hoogeveen EK, Geleijnse JM, Kromhout D, van't Sant P, Gemen EF, Kusters R, Giltay EJ. No effect of n-3 fatty acids supplementation on NT-proBNP after myocardial infarction: the Alpha Omega Trial. Eur J Prev Cardiol. 2015 May;22(5):648-55. doi: 10.1177/2047487314536694. Epub 2014 May 30.
citation: Brouwer IA, Geleijnse JM, Klaasen VM, Smit LA, Giltay EJ, de Goede J, Heijboer AC, Kromhout D, Katan MB. Effect of alpha linolenic acid supplementation on serum prostate specific antigen (PSA): results from the alpha omega trial. PLoS One. 2013 Dec 11;8(12):e81519. doi: 10.1371/journal.pone.0081519. eCollection 2013.
citation: Hoogeveen EK, Geleijnse JM, Kromhout D, Giltay EJ. No effect of n-3 fatty acids on high-sensitivity C-reactive protein after myocardial infarction: the Alpha Omega Trial. Eur J Prev Cardiol. 2014 Nov;21(11):1429-36. doi: 10.1177/2047487313494295. Epub 2013 Jun 17.
citation: Eussen SR, Geleijnse JM, Giltay EJ, Rompelberg CJ, Klungel OH, Kromhout D. Effects of n-3 fatty acids on major cardiovascular events in statin users and non-users with a history of myocardial infarction. Eur Heart J. 2012 Jul;33(13):1582-8. doi: 10.1093/eurheartj/ehr499. Epub 2012 Feb 1.
citation: Kromhout D, Geleijnse JM, de Goede J, Oude Griep LM, Mulder BJ, de Boer MJ, Deckers JW, Boersma E, Zock PL, Giltay EJ. n-3 fatty acids, ventricular arrhythmia-related events, and fatal myocardial infarction in postmyocardial infarction patients with diabetes. Diabetes Care. 2011 Dec;34(12):2515-20. doi: 10.2337/dc11-0896.
citation: Giltay EJ, Geleijnse JM, Kromhout D. Effects of n-3 fatty acids on depressive symptoms and dispositional optimism after myocardial infarction. Am J Clin Nutr. 2011 Dec;94(6):1442-50. doi: 10.3945/ajcn.111.018259. Epub 2011 Oct 26.
citation: Geleijnse JM, Giltay EJ, Kromhout D. Effects of n-3 fatty acids on cognitive decline: a randomized, double-blind, placebo-controlled trial in stable myocardial infarction patients. Alzheimers Dement. 2012 Jul;8(4):278-87. doi: 10.1016/j.jalz.2011.06.002. Epub 2011 Oct 2.
citation: Kromhout D, Giltay EJ, Geleijnse JM; Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010 Nov 18;363(21):2015-26. doi: 10.1056/NEJMoa1003603. Epub 2010 Aug 28.