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

August 24, 2011 updated by: Wageningen University

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

3000

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • VU University Amsterdam, Institute for Health Sciences
      • Rotterdam, Netherlands, 3015 GD
        • Erasmus MC
      • Wageningen, Netherlands
        • Wageningen University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

65 years and older (OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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);

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Fractures
Time Frame: two years
two years

Secondary Outcome Measures

Outcome Measure
Time Frame
Cognitive decline
Time Frame: two years
two years
Bone health
Time Frame: two years
two years
Physical performance
Time Frame: two years
two years
Quality of life
Time Frame: two years
two years
Nutritional status
Time Frame: two years
two years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Wageningen University

Collaborators

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

Investigators

  • Principal Investigator: Lisette CPGM de Groot, Prof, Wageningen University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (ANTICIPATED)

March 1, 2013

Study Completion (ANTICIPATED)

March 1, 2013

Study Registration Dates

First Submitted

June 9, 2008

First Submitted That Met QC Criteria

June 9, 2008

First Posted (ESTIMATE)

June 12, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

August 25, 2011

Last Update Submitted That Met QC Criteria

August 24, 2011

Last Verified

August 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ZonMw 6130.0031
  • NTR1333

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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