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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified August 2011 by Wageningen University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborators:
ZonMw: The Netherlands Organisation for Health Research and Development
MCO Health
Erasmus Medical Center
VU University Medical Center
NZO: Dutch Dairy Association
Information provided by:
Wageningen University
ClinicalTrials.gov Identifier:
NCT00696514
First received: June 9, 2008
Last updated: August 24, 2011
Last verified: August 2011
  Purpose

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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin B12 and Folic Acid Supplementation for Preventing Fractures in Elderly People

Resource links provided by NLM:


Further study details as provided by Wageningen University:

Primary Outcome Measures:
  • Fractures [ Time Frame: two years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Cognitive decline [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Bone health [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Physical performance [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Quality of life [ Time Frame: two years ] [ Designated as safety issue: No ]
  • Nutritional status [ Time Frame: two years ] [ Designated as safety issue: No ]

Estimated Enrollment: 3000
Study Start Date: September 2008
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: March 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00696514

Locations
Netherlands
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
Investigators
Principal Investigator: Lisette CPGM de Groot, Prof Wageningen University
  More Information

No publications provided by Wageningen University

Additional 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, NTR1333
Study First Received: June 9, 2008
Last Updated: August 24, 2011
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Wageningen University:
fracture
cognition

Additional relevant MeSH terms:
Osteoporosis
Cognition Disorders
Bone Diseases, Metabolic
Bone Diseases
Musculoskeletal Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Folic Acid
Vitamin B 12
Hydroxocobalamin
Vitamins
Vitamin B Complex
Hematinics
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents
Hematologic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on July 23, 2014