Condition category
Nutritional, Metabolic, Endocrine
Date applied
12/03/2012
Date assigned
12/04/2012
Last edited
24/08/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Vitamin D helps the body to absorb calcium and phosphorus from the diet and is important for keeping bones healthy. Low vitamin D levels are common in older people in the UK, especially during winter months. Moderate vitamin D deficiency may play a role in causing osteoporosis and fractures and has also been associated with an increased risk of cardiovascular disease, cancer and death. However, it is unclear whether supplementation with vitamin D has any beneficial effects on any of these diseases. Many people in Britain do not get enough sun exposure to maintain what are believed to be healthy vitamin D levels. Only small amounts of vitamin D are derived from food, chiefly from liver and oily fish.

There is substantial uncertainty about the optimal dose of vitamin D to use in large trials testing effects on bone health and other disease outcomes. It is possible that the doses of vitamin D used in previous trials to prevent fractures may have been too low to maintain healthy bones and to demonstrate other health benefits in older people.

The aim of the present study is to determine the optimal daily dose of vitamin D required to maintain blood levels of vitamin D in older people. It will assess the biochemical effects on blood levels of 25-hydroxy-vitamin D (25[OH]D) and parathyroid hormone of different amounts of vitamin D3 daily or a dummy tablet (placebo) when administered for one year.

Who can participate?
About 300 men and women aged 65 or older.

What does the study involve?
Participants will be randomly allocated to take either one of two different doses of vitamin D daily or a matching placebo for a year. The study will examine if these doses are effective at raising blood levels and are safe. The trial will assess the effects of vitamin D on blood levels of 25[OH]D, blood fats (lipids), biomarkers of inflammation, blood pressure, arterial stiffness and bone density. The results of this trial will help to select the optimal dose of vitamin D to be tested in a much larger trial assessing the effects of vitamin D on relevant disease outcomes.

What are the possible benefits and risks of participating?
It is unlikely that participants should gain materially or symptomatically from their participation in the study. However, the information resulting through their participation in the trial will be valuable for planning further larger trials of vitamin D assessing effects on major disease outcomes. The available evidence indicates that the doses of vitamin D used in the trial are likely to be safe and well-tolerated. In the unlikely event of any adverse effects, participants are advised to report any new unexplained symptoms to the study team, whose contact numbers are provided. These symptoms will also be evaluated at each study visit.

Where is the study run from?
The trial is being co-ordinated by the Clinical Trials Service Unit (CTSU), University of Oxford. The trial will be undertaken at a single GP practice, the Hightown Surgery, based in Banbury, Oxfordshire.

When is the study starting and how long is it expected to run for?
The study is expected to start in May 2012, and is anticipated to complete trial procedures by December 2013.

Who is funding the study?
University of Oxford (UK).

Who is the main contact?
Professor Jane Armitage
jane.armitage@ctsu.ox.ac.uk

Trial website

Contact information

Type

Scientific

Primary contact

Prof Jane Armitage

ORCID ID

Contact details

Clinical Trial Service Unit & Epidemiological Studies Unit
University of Oxford
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom
+44(0)1865 743743
jane.armitage@ctsu.ox.ac.uk

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

CTSUBEST-D v 1.0

Study information

Scientific title

Biochemical Efficacy and Safety Trial of vitamin D (BEST-D): a dose-finding trial assessing biochemical and vascular effects of high dose vitamin D

Acronym

BEST-D

Study hypothesis

Null hypothesis
Vitamin D3 in a dose of either 100mcg (4000 IU) or 50mcg (2000 IU) administered for 1 year, will not be sufficient to achieve blood 25(OH)D levels >90 nmol/L, in all older people living in the community.

Ethics approval

Not provided at time of registration

Study design

Double-blind placebo controlled randomised trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Screening

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Safety and efficacy of vitamin D

Intervention

50µg of vitamin D3 or 100 µg of vitamin D3 or matching placebo

Duration: 12 months of treatment

Intervention type

Other

Phase

Not Applicable

Drug names

Primary outcome measures

1. The primary efficacy assessment will involve an “intention-to-treat” analysis among all randomized subjects of daily dietary supplementation with vitamin D3 100 µg vs vitamin D3 50 µg on the proportion of individuals with levels of 25(OH)D above 90 nmol/L at the end of the study.
2. A co-primary endpoint will be the difference between those allocated 100 vs 50 µg daily in the mean 25(OH)D levels at the scheduled study end

Secondary outcome measures

All secondary assessments will involve “intention-to-treat” analyses among all randomized subjects of the effects of daily supplementation with vitamin D3 100µg vs placebo, vitamin D3 50µg vs placebo, and the difference between the two doses of vitamin D on:
1. Mean blood levels of 25(OH)D during follow-up
2. The proportions of participants with blood 25(OH)D levels >90 nmol/L at the 6 and 12 month visits
3. The proportion of participants with PTH levels suppressed into the normal range at the 6 and 12 month visits
4. The proportion of participants with calcium levels above the normal range at the 6 and 12 month visits
5. Other laboratory tests of safety: phosphate, albumin, creatinine, alkaline phosphatase
6. The changes from baseline in hsCRP, creatinine, nBNP, inflammatory cytokines (e.g. IL5, IL6, IL1β, IFNγ and TNFα) at 6 and 12 month visits, and mRNA expression markers of innate immunity at baseline and 12 month visits
7. The difference in the change from baseline in diastolic and systolic blood pressure, heart rate and arterial stiffness at 6 and 12 months
8. The difference in the changes from baseline in total cholesterol, LDL-C, HDL-C, triglycerides, apo-B and apo-A at 12 months

Overall trial start date

30/04/2012

Overall trial end date

30/10/2013

Reason abandoned

Eligibility

Participant inclusion criteria

1. Age ≥ 65 years
2. Living in the community and ambulatory

Participant type

Patient

Age group

Senior

Gender

Both

Target number of participants

300

Participant exclusion criteria

1. Nursing home residents
2. Regular use of vitamin D supplements with >400 IU (10 µg) vitamin D daily
3. Use of alendronate, risedronate, zoledronic acid, parathyroid hormone, or calcitonin
4. Medically diagnosed dementia
5. History of hypercalcaemia, hyperparathyroidism, lymphoma, sarcoidosis, active tuberculosis
6. History of renal calculus
7. Known to be poorly compliant with clinic visits or with taking medication
8. Recent history of alcohol or substance misuse or abuse
9. Medical history that might limit the ability of the subject to take the study treatment for the duration of the study (e.g. terminal illness)
10. Regular prescribed calcium supplements

Recruitment start date

30/04/2012

Recruitment end date

30/10/2013

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Clinical Trial Service Unit & Epidemiological Studies Unit
Oxford
OX3 7LF
United Kingdom

Sponsor information

Organisation

University of Oxford (UK)

Sponsor details

Clinical Trial Service Unit & Epidemiological Studies Unit
Richard Doll Building
Old Road Campus
Roosevelt Drive
Oxford
OX3 7LF
United Kingdom
+44(0)1865 743743
bestd@ctsu.ox.ac.uk

Sponsor type

University/education

Website

http://www.ctsu.ox.ac.uk/

Funders

Funder type

University/education

Funder name

University of Oxford (UK) - Clinical Trials Service Unit (CTSU)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2015 results here: http://www.ncbi.nlm.nih.gov/pubmed/25721698

Publication citations

Additional files

Editorial Notes

24/08/2016: Publication reference added