NCT00696514

Brief Summary

It is hypothesized that vitamin B12 and folic acid supplementation reduces the number of incident fractures. The proposed study, a randomized placebo-controlled intervention trial, compares daily supplementation with folic acid (400 mcg) and vitamin B12 (500 mcg) to a placebo for a period of two years or longer in 3000 men and women aged 70 years and older, with initial basal plasma total homocysteine (tHcy) levels \>= 15 micromol/L. Fracture incidence and time to fracture will be assessed and used as the efficacy measure. Metabolic studies in a sub sample of the population will be included aiming to contribute to an understanding of the biological mechanisms underlying the associations found between markers of B-vitamin status and bone quality.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
3,000

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Sep 2008

Longer than P75 for phase_1

Geographic Reach
1 country

3 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 9, 2008

Completed
3 days until next milestone

First Posted

Study publicly available on registry

June 12, 2008

Completed
3 months until next milestone

Study Start

First participant enrolled

September 1, 2008

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

August 25, 2011

Status Verified

August 1, 2011

Enrollment Period

4.5 years

First QC Date

June 9, 2008

Last Update Submit

August 24, 2011

Conditions

OsteoporosisCognitive Decline

Keywords

fracturecognition

Outcome Measures

Primary Outcomes (1)

  • Fractures

    two years

Secondary Outcomes (5)

  • Cognitive decline

    two years

  • Bone health

    two years

  • Physical performance

    two years

  • Quality of life

    two years

  • Nutritional status

    two years

Study Arms (2)

2

PLACEBO COMPARATOR

placebo capsule, once per day

Dietary Supplement: Placebo (Vitamin D3) - 600 IU per day

1

EXPERIMENTAL

Vitamin B12 and folic acid capsule, once a day

Dietary Supplement: Vitamin B12, folic acid, Vitamin D3

Interventions

Vitamin B12, folic acid, Vitamin D3DIETARY_SUPPLEMENT

500 µg vitamin B12; 0.4 mg folic acid; 600 IU vitamin D3 in one capsule, once per day

1
Placebo (Vitamin D3) - 600 IU per dayDIETARY_SUPPLEMENT

600 IU vitamin D3 in one capsule, once per day

2

Eligibility Criteria

Age65 Years+
Sexall
Healthy VolunteersYes
Age GroupsOlder Adult (65+)

You may qualify if:

  • years and older; based on entry date into study;
  • Fasting plasma Hcy level \>= 12 µmol/L and \< 50 µmol/L;
  • No current or recent (\<4 months) use of supplements with very high doses of B-vitamins;
  • Competent to make own decisions;
  • Persons with skin cancer are allowed to participate.
  • Compliance to tablet intake \> 85%

You may not qualify if:

  • Participation in other intervention trials;
  • Serious medical conditions, e.g. cancer diagnosis within the last 5 years or recent myocardial infarction;
  • Immobilization (bedridden, wheelchair bound);

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (3)

VU University Amsterdam, Institute for Health Sciences

Amsterdam, Netherlands

Location

Erasmus MC

Rotterdam, 3015 GD, Netherlands

Location

Wageningen University

Wageningen, Netherlands

Location

Related Publications (6)

  • van Soest APM, van de Rest O, Witkamp RF, van der Velde N, de Groot LCPGM. The association between adherence to a plant-based diet and cognitive ageing. Eur J Nutr. 2023 Aug;62(5):2053-2062. doi: 10.1007/s00394-023-03130-y. Epub 2023 Mar 11.

    PMID: 36905458DERIVED

  • van Soest APM, van de Rest O, Witkamp RF, Cederholm T, de Groot LCPGM. DHA status influences effects of B-vitamin supplementation on cognitive ageing: a post-hoc analysis of the B-proof trial. Eur J Nutr. 2022 Oct;61(7):3731-3739. doi: 10.1007/s00394-022-02924-w. Epub 2022 Jun 15.

    PMID: 35704085DERIVED

  • Oliai Araghi S, Kiefte-de Jong JC, van Dijk SC, Swart KMA, van Laarhoven HW, van Schoor NM, de Groot LCPGM, Lemmens V, Stricker BH, Uitterlinden AG, van der Velde N. Folic Acid and Vitamin B12 Supplementation and the Risk of Cancer: Long-term Follow-up of the B Vitamins for the Prevention of Osteoporotic Fractures (B-PROOF) Trial. Cancer Epidemiol Biomarkers Prev. 2019 Feb;28(2):275-282. doi: 10.1158/1055-9965.EPI-17-1198. Epub 2018 Oct 19.

    PMID: 30341095DERIVED

  • van Dijk SC, Enneman AW, Swart KM, van Wijngaarden JP, Ham AC, de Jonge R, Blom HJ, Feskens EJ, Geleijnse JM, van Schoor NM, Dhonukshe-Rutten RA, de Jongh RT, Lips P, de Groot LC, Uitterlinden AG, van den Meiracker TH, Mattace-Raso FU, van der Velde N, Smulders YM. Effect of vitamin B12 and folic acid supplementation on biomarkers of endothelial function and inflammation among elderly individuals with hyperhomocysteinemia. Vasc Med. 2016 Apr;21(2):91-8. doi: 10.1177/1358863X15622281. Epub 2016 Jan 15.

    PMID: 26774115DERIVED

  • Brouwer-Brolsma EM, van der Zwaluw NL, van Wijngaarden JP, Dhonukshe-Rutten RA, in 't Veld PH, Feskens EJ, Smeets PA, Kessels RP, van de Rest O, de Groot LC. Higher Serum 25-Hydroxyvitamin D and Lower Plasma Glucose Are Associated with Larger Gray Matter Volume but Not with White Matter or Total Brain Volume in Dutch Community-Dwelling Older Adults. J Nutr. 2015 Aug;145(8):1817-23. doi: 10.3945/jn.115.214197. Epub 2015 Jul 1.

    PMID: 26136594DERIVED

  • van Wijngaarden JP, Dhonukshe-Rutten RA, van Schoor NM, van der Velde N, Swart KM, Enneman AW, van Dijk SC, Brouwer-Brolsma EM, Zillikens MC, van Meurs JB, Brug J, Uitterlinden AG, Lips P, de Groot LC. Rationale and design of the B-PROOF study, a randomized controlled trial on the effect of supplemental intake of vitamin B12 and folic acid on fracture incidence. BMC Geriatr. 2011 Dec 2;11:80. doi: 10.1186/1471-2318-11-80.

    PMID: 22136481DERIVED

MeSH Terms

Conditions

OsteoporosisCognitive DysfunctionFractures, Bone

Interventions

Vitamin B 12Folic AcidCholecalciferol

Condition Hierarchy (Ancestors)

Bone Diseases, MetabolicBone DiseasesMusculoskeletal DiseasesMetabolic DiseasesNutritional and Metabolic DiseasesCognition DisordersNeurocognitive DisordersMental DisordersWounds and Injuries

Intervention Hierarchy (Ancestors)

CorrinoidsTetrapyrrolesPyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingMacrocyclic CompoundsPolycyclic CompoundsPterinsPteridinesHeterocyclic Compounds, 2-RingCholestenesCholestanesSteroidsFused-Ring CompoundsSterolsVitamin DSecosteroidsMembrane LipidsLipids

Study Officials

  • Lisette CPGM de Groot, Prof

    Wageningen University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 9, 2008

First Posted

June 12, 2008

Study Start

September 1, 2008

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

August 25, 2011

Record last verified: 2011-08

Locations

NL(3)