Supplementation with Folate (and vitamins B6 and B12) and/or Omega 3 Fatty Acids on the prevention of recurrent ischaemic events in patients who have already experienced a coronary or cerebrovascular event

ISRCTN ISRCTN41926726
DOI https://doi.org/10.1186/ISRCTN41926726
Protocol serial number N/A
Sponsor INSERM - Direction of Clinical Research (France)
Funders National Institute for Health and Medical Research (INSERM) (France), French National Institute for Agricultural Research (INRA), Ministry of the Higher Education and Research (France), Pierre Fabre, Eprova, Danone Vitapole/Lu, Unilever Bestfoods France, Candia/ Yoplait
Submission date
14/09/2005
Registration date
05/12/2005
Last edited
16/06/2015
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Circulatory System
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Serge Hercberg
Scientific

U557 Inserm (UMR Inserm/Inra/Cnam)
5 rue Vertbois
Paris
75003
France

Study information

Primary study designInterventional
Study designRandomised controlled trial
Secondary study designRandomised controlled trial
Scientific titleSupplementation with Folate (and vitamins B6 and B12) and/or Omega 3 Fatty Acids on the prevention of recurrent ischaemic events in patients who have already experienced a coronary or cerebrovascular event
Study acronymSU.FOL.OM3 Study
Study objectivesDefinitive proof that supplementation with B-vitamins or omega-3 fatty acids will lead to a reduced cardiovascular diseases morbidity and/or mortality is still scarce. The currently available intervention trials did either not have a study design that allows this conclusion or the results need to be reproduced before they can be regarded as definitive. (NB the trials with B vitamins evaluated mostly the effect on intermediate end-points).

Secondary intervention trials with hard endpoints and B-vitamin supplementation have recently started, but not all of these trials used a combination B vitamins and most trials used pharmacological doses. This has the disadvantage that the results will be difficult to translate into dietary advice. In addition, recent research has indicated that supplementation with 5-methyl tetrahydrofolate (5-methyl-THF), the most abundant natural folate vitamin, is safe and lowers homocysteine levels. This form of folate, in contrast to folic acid, does not lead to circulating unmetabolized folic acid. Unmetabolized folic acid is hypothesized to mask the hematological manifestations of a vitamin B12 deficiency, thereby predisposing subjects to irreversible neurological damage. Stable 5-methyl-THF was not available when other intervention studies started and therefore they all use folic acid.

Taking all this information together, there is a need for a large double-blind placebo-controlled randomized intervention trial evaluating the effect of supplementation with B-vitamins (exchanging folic acid for 5-methyl-THF) and n-3 fatty acids in nutritional doses on hard cardiovascular endpoints. Therefore, we propose the following intervention study in which participants are SUpplemented with natural FOLate, vitamin B6 and B12 and/or OMega-3 fatty acids: the SU.FOL.OM3 study.
Ethics approval(s)1. Ethics Committee of Paris-Cochin (Comité Consultatif pour la Protection des Personnes se prêtant à la Recherche Biomédicale) (ref: CCPPRB n°1933)
2. National Committee of information and liberty (La Commission Nationale de l'Informatique et des Libertés [CNIL]) (ref: CNIL n° 901230)
Health condition(s) or problem(s) studiedCardio and neurovascular diseases
Intervention5-methyl-THF (560 µg), vitamin B6 (3 mg) and B12 (20 µg) and/or omega-3 supplements (600 mg with an eicosapentaenoic acid [EPA]:docosahexaenoic acid [DHA] ratio of 2:1) versus placebo
Intervention typeSupplement
Primary outcome measure(s)

Combination of myocardial infarction, cerebral vascular ischemic accident or cardiovascular deaths

Key secondary outcome measure(s)

1. Hospitalisation for coronary diseases
2. Hospitalisation for cardiac diseases
3. Hospitalisation for vascular diseases
4. Total mortality
5. Cardiovascular mortality
6. Myocardial infarctions
7. Acute coronary syndrome without necrosis
8. Ischemic cerebral vascular accidents
9. Arteriopathies
10. Venous thrombosis
11. Cancers

Completion date30/06/2009

Eligibility

Participant type(s)Patient
Age groupAdult
SexAll
Target sample size at registration2400
Key inclusion criteria1. Participants should have experienced a coronary or cerebral event during 1 to 12 months before baseline. A coronary or cerebral event is defined as:
a. Myocardial infarction (validated and documented by a combination of clinical, enzymatic, or electrocardiogram [ECG] parameters)
b. Acute coronary syndrome without necrosis (validated and documented by a combination of clinical, enzymatic or ECG parameters)
c. A cerebral vascular ischemic accident (defined by criteria validated in epidemiological studies)
2. The participants should be 45-80 years at baseline
Key exclusion criteria1. Age <45 years or >80 years
2. Cardiovascular pathology not well defined
3. Patients that are incapable of understanding the study protocol
4. Patients with a pathology that might interfere with homocysteine or omega-3 fatty acid metabolism, in particular those that use methotrexate for the treatment of a cancer or rheumatoid arthritis and chronic renal failure (plasma level of creatinine >200 µmol/l or creatinine clearance <40 ml/min)
5. Patients with a non-cardiovascular pathology with a suspected survival time less than the 5 years period of the study (solid cancer, evolved dementia, leukemia etc.)
Date of first enrolment15/04/2003
Date of final enrolment30/06/2009

Locations

Countries of recruitment

  • France

Study participating centre

U557 Inserm (UMR Inserm/Inra/Cnam)
Paris
75003
France

Results and Publications

Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot provided at time of registration
IPD sharing plan

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Results article results 29/11/2010 Yes No
Results article blood pressure results 01/03/2012 Yes No
Results article cancer prevention results 09/04/2012 Yes No
Results article depressive symptoms results 01/07/2012 Yes No
Results article biomarker results 01/06/2013 Yes No
Results article baseline plasma fatty acids profile results 07/04/2014 Yes No
Protocol article protocol 10/06/2008 Yes No
Other publications publication on background and rationale of the SU.FOL.OM3 study 01/02/2003 Yes No
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