Name:

Vitamin D trial

Parent study:

N/A

Other names:

A randomised, double blind, placebo controlled, phase II, multi-centre pilot study to investigate the effects of vitamin D2 or D3 supplementation on metabolic parameters in people at risk of type 2 diabetes.

Description:

In a double-blind placebo-controlled randomized trial, 340 adults who had an elevated risk of type 2 diabetes (non-diabetic hyperglycaemia or positive diabetes risk score) were randomized to either placebo, 100 000 IU vitamin D2 (ergocalciferol) or 100 000 IU vitamin D3 (cholecalciferol), orally administered monthly for 4months. The primary outcome was change in glycated haemoglobin (HbA1c) between baseline and 4months, adjusted for baseline. Secondary outcomes included: blood pressure; lipid levels; apolipoprotein levels; C-reactive protein levels; pulse wave velocity (PWV); anthropometric measures; and safety of the supplementation.

Abstract:

The mean [standard deviation (s.d.)] 25-hydroxyvitamin D [25(OH)D]2 concentration increased from 5.2 (4.1) to 53.9 (18.5) nmol/l in the D2 group, and the mean (s.d.) 25(OH)D3 concentration increased from 45.8 (22.6) to 83.8 (22.7) nmol/l in the D3 group. There was no effect of vitamin D supplementation on HbA1c: D2 versus placebo: −0.05% [95% confidence interval (CI) −0.11, 0.02] or −0.51 mmol/mol (95% CI −1.16, 0.14; p=0.13); D3 versus placebo: 0.02% (95% CI −0.04, 0.08) or 0.19 mmol/mol (95% CI −0.46, 0.83; p=0.57). There were no clinically meaningful effects on secondary outcomes, except PWV [D2 versus placebo: −0.68 m/s (95% CI −1.31, −0.05); D3 versus placebo −0.73 m/s (95% CI −1.42, −0.03)]. No important safety issues were identified.

Locations:

The london Centre	The Cambridge Centre

Keywords:

Intervention, placebo, pulse wave velocity, randomized, trial, type 2 diabetes, vitamin D2, vitamin D3.

Research areas:

Diabetes

Research purposes:

To investigate the effect of short-term vitamin D supplementation on cardiometabolic outcomes among individuals with an elevated risk of diabetes.

Population:

Men and women aged 3075 years registered with a general practitioner (London) or already part of the Fenland study (Cambridge), from any ethnic group were eligible if they had an elevated risk of developing type 2 diabetes, with either: (i) the presence of non-diabetic hyperglycaemia defined by either impaired glucose tolerance or impaired fasting glucose (World Health Organization criteria), or glycated haemoglobin (HbA1c) levels of 5.56.49% (3747mmol/mol) or (ii) the presence of Cambridge Risk Score thresholds that indicate elevated risk of diabetes.

Status:

Completed

Recruitment:

Closed to recruitment, participants were 340 adults (172 from Cambridge & 168 from London) at raised risk of T2D.

Start date:

2009/Dec/22

End date:

2013/Mar/0

Links:

Title	URL
Study website	http://www.mrc-epid.cam.ac.uk/research/studies/vitamin-d-trial/

Identifiers:

Identifier	Description
European Clinical Trials Database (EudraCT) number	2009-011264-11
	ISRCTN86515510

Approval:

Title	Details
REC ref: 09/H0711/85	Charing Cross Research Ethics Committee. Favourable opinion received 22/12/2009

Funding required:

Funding	Details
MC_UP_A100_1003, MC_U106179474, MC_UU_12015/5 and MC_UU_12015/4	The trial was funded from a block grant from the NHS Tower Hamlets Primary Care NHS Trust and East London CLRN, and from MRC Epidemiology Unit core funding.

Data access:

Data requests are submitted to the Vitamin D Trial steering committee (TSC) for approval. A Data Request Form for submission to the VitD TSC is available and once completed should be sent in the first instance to datasharing@mrc-epid (or alternatively please print, complete, scan and submit using this PDF). The UNIT Senior Data Manager, Adam Dickinson, will manage the processing of your data request.

Data collected:

The primary outcome was change in glycated haemoglobin (HbA1c) level between baseline and 4 months. Secondary outcome measures included blood pressure, anthropometry (body mass index and waist circumference), fructosamine, lipid and apolipoprotein levels, liver function tests, C-reactive protein level and safety of supplementation. At the London site we also included a measure of pulse wave velocity (PWV).

Sample size:

340 (114 placebo, 112 D2, 114 D3)

Sampling method:

Eligible participants were identified from GPs or the ongoing Fenland study

Participation type:

Written informed consent obtained from all participants

Inclusion criteria:

Men and women aged 3075 years, from any ethnic group, who can provide informed consent for participation in the trial and are at a high risk of developing type 2 diabetes were included.

Risk of developing diabetes was defined by the following criteria:

1. Non-diabetic hyperglycaemia; either impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) as defined by current World Health Organisation (WHO) criteria, or HbA1c between 5.5% and 6.49% (equivalent to 37 to 47 mmol/mol), where this information was available in medical records (London), or in the records of studies in which the participants have consented to being re-approached to consider participating in future studies (Cambridge), or,
2. Cambridge Risk Score (CRS) [38-41] cut-offs that indicate increased risk for diabetes. The CRS cut-offs are 0.236 for the Black/Caribbean population, 0.127 for South Asians and 0.199 for Caucasians. For other groups the cut-off for Caucasians was used. This approach was used at the London site.

Exclusion criteria:

Participants were excluded if they had a known history of diabetes or used oral hypoglycaemic agents, had random blood glucose during initial screening >11 mmol/l, had known intolerance to vitamin D2 or D3 within the previous two months or were using vitamin D supplements, had a known history of hypercalcaemia (serum calcium >2.65 mmol/l) or point of care ionised calcium >1.3 mmol/l. They were also excluded if they have known stage 4 or worse chronic kidney disease (eGFR (estimated glomerular filtration rate) < 30 ml/min), a history of significant liver disease (AST (aspartate aminotransferase) >3 x upper limit of normal (ULN) or ALT (Alanine aminotransferase) >3 x upper limit of normal (ULN) or serum bilirubin > 2.5 x ULN), a known history of renal stones, hyperparathyroidism, active sarcoidosis, tuberculosis or malignancy (active defined as currently on treatment and/or medication for the above conditions), had taken cardiac glycosides or oral/ intramuscular/intravenous corticosteroids (excluding inhaled and topical corticosteroids) in the past one month. They were excluded if they have known current anaemia (haemoglobin <11 g/dL) or haemoglobinopathy such as sickle cell anaemia and beta or alpha thalassemia. Additionally, if they planned to travel out of the London or Cambridge area (depending on site of recruitment) within 8 weeks of enrolment such that it would disrupt monitoring of the participant, they were excluded. Among women, current breast feeding, pregnancy or planning a pregnancy were also considered exclusion criteria.

Follow up:

Trial visits at Day 1, 1 month, 2 months and 4 months. Telephone call at 3 months.

Current size:

342

Accountable people:

Principal investigators, directors and leads of projects

Role	Name (follow link for contact details)
Chief Investigator	Prof Graham Hitman
Principle Investigator	Professor Nita Gandhi Forouhi
Principle Investigator	Prof Christopher Griffiths
Principle Investigator	Professor Nick Wareham
Principle Investigator	Professor Simon Griffin
Principle Investigator	Dr Douglas Russell
Clinical Co-principal Investigator	Prof Stephen Greenwald
Clinical Co-principal Investigator Investigator	Dr Adrian Martineau
Clinical Co-Investigator	Dr Tahseen Chowdhury
Consultant	Dr Barbara Boucher
Clinical Laboratory Investigator	Dr Peter Timms
Clinical Investigator, Trial Coordinator and study monitor (London)	Dr Ravi Menon
Study Statistician	Stephen Sharp
Clinical Research Manager	Gwen Brierley
Senior Data Manager	Adam Dickinson

Methods of contact:

Post, email, phone

Data sources:

• Access overview study details by following the OVERVIEW link for a study
• Access the details of a studies data and releases by following the RELEASE link for a study
• Access the latest study data dictionary by following the DICTIONARY link for a study
• Access the study questionaiires by following the QUESTIONNAIRES link for a study

OVERVIEW

RELEASE

DICTIONARY

QUESTIONAIRES

Related parties:

N/A

Additional information:

Trial results paper:

Forouhi NG, Menon RK, Sharp SJ, et al. Effects of vitamin D2 or D3 supplementation on glycaemic control and cardiometabolic risk among people at risk of type 2 diabetes: results of a randomized double-blind placebo-controlled trial. Diabetes, obesity & metabolism 2016;18:392-400.

Trial protocol paper:

Menon RK, Rickard AP, Mannan N, Timms PM, Sharp SJ, et al. (2013) The effects of vitamin D2 or D3 supplementation on glycaemic control and related metabolic parameters in people at risk of type 2 diabetes: protocol of a randomised double-blind placebo-controlled trial. BMC Public Health 13: 999.

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Information created: 19th April 2017 by A Dickinson

Information last updated: 19th April 2017 by A Dickinson