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

Sponsor

Wageningen University (Other)

Overall Status

Unknown status

CT.gov ID

NCT00696514

Collaborator

ZonMw: The Netherlands Organisation for Health Research and Development (Other), MCO Health (Other), Erasmus Medical Center (Other), Amsterdam UMC, location VUmc (Other), NZO: Dutch Dairy Association (Other)

3,000

Enrollment

Locations

Arms

53.9

Duration (Months)

1000

Patients Per Site

18.5

Patients Per Site Per Month

Study Details

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

Anticipated 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 :

Sep 1, 2008

Anticipated Primary Completion Date :

Mar 1, 2013

Anticipated Study Completion Date :

Mar 1, 2013

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

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

Fractures [two years]

Secondary Outcome Measures

Cognitive decline [two years]
Bone health [two years]
Physical performance [two years]
Quality of life [two years]
Nutritional status [two years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

65 Years and Older

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

Locations

	Site	City	Country	Postal Code
1	VU University Amsterdam, Institute for Health Sciences	Amsterdam	Netherlands
2	Erasmus MC	Rotterdam	Netherlands	3015 GD
3	Wageningen University	Wageningen	Netherlands