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OsteoporosisPhase 1B-PROOFNCT00696514

Vitamin B12 and Folic Acid Supplementation for Preventing Fractures in Elderly People

A Phase 1 study testing Vitamin B12, folic acid, Vitamin D3 in people with Osteoporosis and Cognitive Decline, run by Wageningen University at 3 sites in Netherlands.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial 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… Read more about this study

Who is it for?
Ages 65 years and olderHealthy volunteers can take part
Conditions the study is for
Osteoporosis, Cognitive Decline
What is being tested?
Vitamin B12, folic acid, Vitamin D3
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
3,000 participants
Where
3 sitesNetherlands
Study dates
Sep 2008to Mar 2013
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 65 years and older
  • All sexes
  • Healthy volunteers accepted
  • Older adult

Who may be able to join

  • 65 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%

Who cannot join

  • 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);

Trial locations and contacts

3 sites in 1 country.

Netherlands3 sites

  • VU University Amsterdam, Institute for Health Sciences

    Amsterdam

  • Erasmus MC

    Rotterdam, 3015 GD

  • Wageningen University

    Wageningen

Other trials in Netherlands

About this study

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.

Read the detailed description

Rationale: There is growing evidence that an elevated homocysteine level is a risk factor for fracture incidence. The most common cause of homocysteine elevation is poor vitamin B12 and folate status. It is hypothesized that supplementation with 500 µg vitamin B12 and 400 µg folic acid will reduce fracture incidence in elderly people Main objective: to determine the efficacy of oral supplementation with vitamin B12 and folic acid in the prevention of fractures Study design: The trial is a randomized double-blind placebo-controlled trial, with two arms in parallel (placebo versus supplement). The intervention comprises a period of two years, and will be targeted to 3000 elderly subjects with elevated homocysteine levels. The study will be performed in institutions or residences for older persons around Wageningen, Rotterdam and Amsterdam.

Study population: 3000 elderly subjects (70 years and older) with elevated homocysteine levels Intervention (if applicable): One group receives daily a tablet with 500 µg vitamin B12 and 400 ug folic acid and the other group receives daily a placebo tablet. In both tablets 15 µg (600 IU) of vitamin D is included as well.

Main study parameters/endpoints: Fracture incidence is the primary outcome measure Time to fracture will be calculated. It is expected that in the intervention group 34% less fractures will occur than in the placebo group.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: First, participants need to be recruited. This will be done via information letters. Those who are interested have to complete a small questionnaire and then they will receive an information brochure. Upon continued interest in the intervention study, participants will be invited for a blood sampling. This blood sampling will take place (nearby or) at the location where the participants live. Immediately after the blood sampling a run-in period will start. Blood will be checked on homocysteine levels. Only participants with elevated levels of homocysteine will be included in the study. Two to four weeks after the run-in period the intervention study will be implemented. At the start of this intervention study several measurements will be performed and several questionnaires will be completed together with the participant at home. During the whole study participants need to take daily one tablet and they have to complete calenders to monitor fracture incidence. At the end of the study, blood sampling will be performed and several measurements and questionnaires will be repeated again at home.

Being tested
Vitamin B12, folic acid, Vitamin D3, Placebo (Vitamin D3) - 600 IU per day
Keywords
fracture, cognition
Medical subject headings
Osteoporosis, Cognitive Dysfunction, Fractures, Bone

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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

  • Placebo (Vitamin D3) - 600 IU per dayDietary supplement

    600 IU vitamin D3 in one capsule, once per day

Study groups in NCT00696514
Study groupRoleWhat they receive
2Placebo comparatorplacebo capsule, once per day
Receives: Dietary Supplement: Placebo (Vitamin D3) - 600 IU per day
1ExperimentalVitamin B12 and folic acid capsule, once a day
Receives: Dietary Supplement: Vitamin B12, folic acid, Vitamin D3

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Fractures

    Measured: two years

Secondary outcomes (5)

  1. Cognitive decline

    Measured: two years

  2. Bone health

    Measured: two years

  3. Physical performance

    Measured: two years

  4. Quality of life

    Measured: two years

  5. Nutritional status

    Measured: two years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2008 (estimated)
  2. Study startSep 2008
  3. Primary completionMar 2013 (estimated)
  4. Study completionMar 2013 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
3,000 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00696514
Sponsor's protocol ID
ZonMw 6130.0031
Other IDs
NTR1333
Acronym
B-PROOF
Status last verified
Aug 2011
First submitted
9 Jun 2008
Last updated
25 Aug 2011
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 36905458

  • 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.

    PubMed 35704085

  • 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.

    PubMed 30341095

  • 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.

    PubMed 26774115

  • 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.

    PubMed 26136594

  • 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.

    PubMed 22136481

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vitamin B12, folic acid, Vitamin D3 in people with Osteoporosis and Cognitive Decline, run by Wageningen University at 3 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 25 Aug 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fractures (time frame: two years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00696514, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Aug 2011; AzTrials last refreshed its copy on 8 Nov 2026.

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