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Vitamin B12 and Folic Acid Supplementation for Preventing Fractures in Elderly People (B-PROOF)

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ClinicalTrials.gov Identifier: NCT00696514
Recruitment Status : Unknown
Verified August 2011 by Wageningen University.
Recruitment status was:  Active, not recruiting
First Posted : June 12, 2008
Last Update Posted : August 25, 2011
Information provided by:

Study Description
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.

Condition or disease Intervention/treatment Phase
Osteoporosis Cognitive Decline Dietary Supplement: Vitamin B12, folic acid, Vitamin D3 Dietary Supplement: Placebo (Vitamin D3) - 600 IU per day Phase 1

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.

Study Design

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 3000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin B12 and Folic Acid Supplementation for Preventing Fractures in Elderly People
Study Start Date : September 2008
Estimated Primary Completion Date : March 2013
Estimated Study Completion Date : March 2013

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
Placebo Comparator: 2
placebo capsule, once per day
Dietary Supplement: Placebo (Vitamin D3) - 600 IU per day
600 IU vitamin D3 in one capsule, once per day
Experimental: 1
Vitamin B12 and folic acid capsule, once a day
Dietary Supplement: Vitamin B12, folic acid, Vitamin D3
500 µg vitamin B12; 0.4 mg folic acid; 600 IU vitamin D3 in one capsule, once per day

Outcome Measures

Primary Outcome Measures :
  1. Fractures [ Time Frame: two years ]

Secondary Outcome Measures :
  1. Cognitive decline [ Time Frame: two years ]
  2. Bone health [ Time Frame: two years ]
  3. Physical performance [ Time Frame: two years ]
  4. Quality of life [ Time Frame: two years ]
  5. Nutritional status [ Time Frame: two years ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   65 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Inclusion Criteria:

  • 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%

Exclusion Criteria:

  • 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);
Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00696514

VU University Amsterdam, Institute for Health Sciences
Amsterdam, Netherlands
Erasmus MC
Rotterdam, Netherlands, 3015 GD
Wageningen University
Wageningen, Netherlands
Sponsors and Collaborators
Wageningen University
ZonMw: The Netherlands Organisation for Health Research and Development
MCO Health
Erasmus Medical Center
VU University Medical Center
NZO: Dutch Dairy Association
Principal Investigator: Lisette CPGM de Groot, Prof Wageningen University
More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: ZonMw: The Netherlands Organisation for Health Research and Development
ClinicalTrials.gov Identifier: NCT00696514     History of Changes
Other Study ID Numbers: ZonMw 6130.0031
First Posted: June 12, 2008    Key Record Dates
Last Update Posted: August 25, 2011
Last Verified: August 2011

Keywords provided by Wageningen University:

Additional relevant MeSH terms:
Cognitive Dysfunction
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Metabolic Diseases
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Vitamin D
Folic Acid
Vitamin B 12
Vitamin B Complex
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents