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 |
| Secondary identifying numbers | N/A |
- 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
Not provided at time of registration
Contact information
Prof Serge Hercberg
Scientific
Scientific
U557 Inserm (UMR Inserm/Inra/Cnam)
5 rue Vertbois
Paris
75003
France
Study information
| Study design | Randomised controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Not specified |
| Study type | Prevention |
| Scientific title | 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 |
| Study acronym | SU.FOL.OM3 Study |
| Study hypothesis | Definitive 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) |
| Condition | Cardio and neurovascular diseases |
| Intervention | 5-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 type | Supplement |
| Primary outcome measure | Combination of myocardial infarction, cerebral vascular ischemic accident or cardiovascular deaths |
| Secondary outcome measures | 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 |
| Overall study start date | 15/04/2003 |
| Overall study end date | 30/06/2009 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Sex | Both |
| Target number of participants | 2,400 |
| Participant inclusion criteria | 1. 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 |
| Participant exclusion criteria | 1. 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.) |
| Recruitment start date | 15/04/2003 |
| Recruitment end date | 30/06/2009 |
Locations
Countries of recruitment
- France
Study participating centre
U557 Inserm (UMR Inserm/Inra/Cnam)
Paris
75003
France
75003
France
Sponsor information
INSERM - Direction of Clinical Research (France)
Research organisation
Research organisation
101 rue de Tolbiac
Paris
75003
France
| Website | http://www.inserm.fr |
|---|---|
"ROR" |
https://ror.org/02vjkv261 |
Funders
Funder type
Industry
National Institute for Health and Medical Research (INSERM) (France)
No information available
French National Institute for Agricultural Research (INRA)
No information available
Ministry of the Higher Education and Research (France)
No information available
Pierre Fabre
No information available
Eprova
No information available
Danone Vitapole/Lu
No information available
Unilever Bestfoods France
No information available
Candia/ Yoplait
No information available
Results and Publications
| Intention to publish date | |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| Publication and dissemination plan | Not provided at time of registration |
| IPD sharing plan |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Other publications | publication on background and rationale of the SU.FOL.OM3 study | 01/02/2003 | Yes | No | |
| Protocol article | protocol | 10/06/2008 | Yes | No | |
| 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 |
