NORVIT and WENBIT - Long-term Follow-up

NCT00671346 | Unknown

• 4 other identifiers: NSD-17895REK-267.07DT-08/00230-2/RVBHdir-08/623-
• Study Type: observational
• Target: 6,839
• Locations: 1 country
• Sites: 2

Brief Summary

Two large homocysteine-lowering B-vitamin intervention trials have been performed in Norway during the period 1998 to 2005, NORVIT and WENBIT. The main objective in these trials was to study the clinical effects of homocysteine-lowering therapy with folic acid and vitamin B12 in patients with established coronary artery disease. Follow-up was terminated for NORVIT on Marc 31st 2004 and for WENBIT October 5th 2005, and none of the two trials proved any protective effect of the B-vitamin intervention on cardiovascular outcomes. There is so far no data on possible long-term effects following years of such B-vitamin treatment. Thus, the main objective of the combinded NORVIT-WENBIT study will will be to evaluate the long-term effect of the B-vitamin intervention on incident life-style diseases including cardiovascular disease, diabetes, osteoporotic fractures and cancer. A secondary object will be the identification of risk phenotypes or genotypes, and if such risk associations are midified by the B-vitamin intervention

Conditions

Cancer; Myocardial Infarction; Cerebrovascular Stroke

Keywords

Cancer; Coronary artery disease; Myocardial infarction; Cerebrovascular stroke; Homocysteine; Vitamin B Complex; Folic acid; Vitamin B12; Vitamin B6; Pyridoxal phosphate; Osteoporotic fractures; Diabetes

Outcome Measures

Primary Outcomes (1)

• Possible effects of B-vitamin treatment on risk of developing cancer during the trial periods (completed by 2004 and 2005) and during post-trial follow-up.

  1998-2014

Secondary Outcomes (1)

• The possible effects of B-vitamin treatment on major cardiovascular events, all cause mortality and cause specific death during the trial periods (completed by 2004 and 2005) and during post-trial follow-up.

  1998-2014

Study Arms (4)

1

Participants in NORVIT and WENBIT allocated to daily oral treatment with folic acid 0.8 mg and vitamin B12 0.4 mg

2

Participants in NORVIT and WENBIT allocated to daily oral treatment with folic acid 0.8 mg, vitamin B12 0.4 mg and B6 40 mg.

3

Participants in NORVIT and WENBIT allocated to daily oral treatment with vitamin B6 40 mg.

4

Participants in NORVIT and WENBIT allocated to daily oral treatment with placebo

Eligibility Criteria

• Age: 27 Years - 86 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study population for combined analyses consists of the of 3 749 + 3 090 = 6 839 men and women aged 27 - 86 years when randomised in the NORVIT and WENBIT trials between December 1998 and April 2004. All patients in NORVIT were randomised following an acute myocardial infarction, whereas patients in WENBIT were randomised following coronary angiography, of which 85% had stable angina pectoris, 10% had acute myocardial infarction and 5% had unstable angina pectoris at baseline.

You may qualify if:

• Randomised in the Norwegian Vitamin Trial (NORVIT) or in the Western Norway B-Vitamin Intervention Trial (WENBIT)

You may not qualify if:

• Withdrawn consent to participate in study cohort for post-trial observational follow-up

Sponsors & Collaborators

• Haukeland University Hospital: lead
• University of Tromso: collaborator
• Norwegian Foundation for Health and Rehabilitation: collaborator

Study Sites (2)

Department of Heart Disease, Haukeland University Hospital

Bergen, 5021, Norway

Location

University of Tromsø

Tromsø, 9037, Norway

Location

Related Publications (14)

• Bonaa KH, Njolstad I, Ueland PM, Schirmer H, Tverdal A, Steigen T, Wang H, Nordrehaug JE, Arnesen E, Rasmussen K; NORVIT Trial Investigators. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006 Apr 13;354(15):1578-88. doi: 10.1056/NEJMoa055227. Epub 2006 Mar 12.

  PMID: 16531614 BACKGROUND

• Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006 Dec 13;296(22):2720-6. doi: 10.1001/jama.296.22.2720.

  PMID: 17164458 BACKGROUND

• Clarke R, Armitage J, Lewington S, Collins R; B-Vitamin Treatment Trialists' Collaboration. Homocysteine-lowering trials for prevention of vascular disease: protocol for a collaborative meta-analysis. Clin Chem Lab Med. 2007;45(12):1575-81. doi: 10.1515/CCLM.2007.346.

  PMID: 18265450 BACKGROUND

• Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Stenling R, Riboli E, Winkvist A, Palmqvist R. Low folate levels may protect against colorectal cancer. Gut. 2006 Oct;55(10):1461-6. doi: 10.1136/gut.2005.085480. Epub 2006 Apr 25.

  PMID: 16638790 BACKGROUND

• Hultdin J, Van Guelpen B, Bergh A, Hallmans G, Stattin P. Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study. Int J Cancer. 2005 Feb 20;113(5):819-24. doi: 10.1002/ijc.20646.

  PMID: 15499634 BACKGROUND

• Cole BF, Baron JA, Sandler RS, Haile RW, Ahnen DJ, Bresalier RS, McKeown-Eyssen G, Summers RW, Rothstein RI, Burke CA, Snover DC, Church TR, Allen JI, Robertson DJ, Beck GJ, Bond JH, Byers T, Mandel JS, Mott LA, Pearson LH, Barry EL, Rees JR, Marcon N, Saibil F, Ueland PM, Greenberg ER; Polyp Prevention Study Group. Folic acid for the prevention of colorectal adenomas: a randomized clinical trial. JAMA. 2007 Jun 6;297(21):2351-9. doi: 10.1001/jama.297.21.2351.

  PMID: 17551129 BACKGROUND

• Charles D, Ness AR, Campbell D, Davey Smith G, Hall MH. Taking folate in pregnancy and risk of maternal breast cancer. BMJ. 2004 Dec 11;329(7479):1375-6. doi: 10.1136/bmj.329.7479.1375. No abstract available.

  PMID: 15591563 BACKGROUND

• Mason JB, Dickstein A, Jacques PF, Haggarty P, Selhub J, Dallal G, Rosenberg IH. A temporal association between folic acid fortification and an increase in colorectal cancer rates may be illuminating important biological principles: a hypothesis. Cancer Epidemiol Biomarkers Prev. 2007 Jul;16(7):1325-9. doi: 10.1158/1055-9965.EPI-07-0329.

  PMID: 17626997 BACKGROUND

• Ulrich CM, Potter JD. Folate and cancer--timing is everything. JAMA. 2007 Jun 6;297(21):2408-9. doi: 10.1001/jama.297.21.2408. No abstract available.

  PMID: 17551134 BACKGROUND

• Ebbing M, Bleie O, Ueland PM, Nordrehaug JE, Nilsen DW, Vollset SE, Refsum H, Pedersen EK, Nygard O. Mortality and cardiovascular events in patients treated with homocysteine-lowering B vitamins after coronary angiography: a randomized controlled trial. JAMA. 2008 Aug 20;300(7):795-804. doi: 10.1001/jama.300.7.795.

  PMID: 18714059 BACKGROUND

• Ebbing M, Bonaa KH, Nygard O, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njolstad I, Refsum H, Nilsen DW, Tverdal A, Meyer K, Vollset SE. Cancer incidence and mortality after treatment with folic acid and vitamin B12. JAMA. 2009 Nov 18;302(19):2119-26. doi: 10.1001/jama.2009.1622.

  PMID: 19920236 RESULT

• Ulvik A, Ebbing M, Hustad S, Midttun O, Nygard O, Vollset SE, Bonaa KH, Nordrehaug JE, Nilsen DW, Schirmer H, Ueland PM. Long- and short-term effects of tobacco smoking on circulating concentrations of B vitamins. Clin Chem. 2010 May;56(5):755-63. doi: 10.1373/clinchem.2009.137513. Epub 2010 Mar 18.

  PMID: 20299681 RESULT

• Ebbing M, Bonaa KH, Arnesen E, Ueland PM, Nordrehaug JE, Rasmussen K, Njolstad I, Nilsen DW, Refsum H, Tverdal A, Vollset SE, Schirmer H, Bleie O, Steigen T, Midttun O, Fredriksen A, Pedersen ER, Nygard O. Combined analyses and extended follow-up of two randomized controlled homocysteine-lowering B-vitamin trials. J Intern Med. 2010 Oct;268(4):367-82. doi: 10.1111/j.1365-2796.2010.02259.x.

  PMID: 20698927 RESULT

• Zuo H, Svingen GFT, Tell GS, Ueland PM, Vollset SE, Pedersen ER, Ulvik A, Meyer K, Nordrehaug JE, Nilsen DWT, Bonaa KH, Nygard O. Plasma Concentrations and Dietary Intakes of Choline and Betaine in Association With Atrial Fibrillation Risk: Results From 3 Prospective Cohorts With Different Health Profiles. J Am Heart Assoc. 2018 Apr 12;7(8):e008190. doi: 10.1161/JAHA.117.008190.

  PMID: 29650710 DERIVED

Related Links

• NORVIT on ClinicalTrials.gov
• WENBIT on ClinicalTrials.gov

MeSH Terms

Conditions

Neoplasms; Myocardial Infarction; Stroke; Coronary Artery Disease; Osteoporotic Fractures; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Coronary Disease; Arteriosclerosis; Arterial Occlusive Diseases; Fractures, Bone; Wounds and Injuries; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Ottar Nygård, MD, PhD

  Department of Heart Disease, Haukeland University Hospital

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: April 29, 2008
• First Posted: May 5, 2008
• Study Start: December 1, 1998
• Primary Completion: December 1, 2020
• Study Completion: January 1, 2021
• Last Updated: November 5, 2015

Record last verified: 2015-11

Locations

NO (2)