Vitamin D therapy to reduce cardiovascular risk in type two diabetes - the next steps

ISRCTN	ISRCTN50587697
DOI	https://doi.org/10.1186/ISRCTN50587697
EudraCT/CTIS number	2007-003767-51
Secondary identifying numbers	2006DM18

Submission date: 11/07/2007
Registration date: 27/09/2007
Last edited: 26/02/2018

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Small studies have shown that vitamin D, a hormone that the skin usually makes using sunshine, may be able to reduce blood pressure and improve blood vessel health in people with type 2 diabetes. It is not clear what the best dose of vitamin D to use is, or how long the effect of a single large dose lasts for.
The aim of the study is therefore to compare the effect of two different doses of vitamin D with placebo (dummy) and measure whether an effect on blood vessel health and blood pressure can be seen at 8 and 16 weeks after the dose.
Who can participate?
Adults aged 18 years and older with type 2 diabetes

What does the study involve?
The study lasts for 16 weeks. At the start, participants are randomly allocated to one of three groups. They receive two teaspoons of oil, which will contain either 100,000 units vitamin D3, 200,000 units vitamin D3, or a matching placebo (dummy).
Participants are assessed at the start, and 8 weeks and 16 weeks. Each visit lasts 1.5 hours.
At each visit, participants receive some or all of the following depending on which visit it is:
-Blood pressure measurement
-Blood sample taken
-Test the function of the artery in their arm. The artery is scanned with an ultrasound machine before and after inflating a blood pressure cuff on their forearm for 5 minutes. The test is repeated after the participant is given a medication (GTN) spray under their tongue
-Wear a blood pressure cuff and a heart rate monitor (ECG) for 24 hours including at home.

What are the possible benefits and risks of participating?
Although participants are unlikely to benefit directly by taking part in the trial, those who receive the vitamin D might find that blood pressure is lowered.
Although this dose of vitamin D has been used before and is known to be safe there is a small possibility of side effects. Participants are closely monitored for side effects caused by high calcium levels: sickness, diarrhoea, thirst or dizziness. To reduce the chance of vitamin D increasing the calcium level in their blood, participants are also asked not to take vitamin D supplements or calcium supplements whilst taking part in this study.
Having blood taken can cause some bruising. The blood pressure cuff causes mild discomfort to some people.

Where is the study run from?
Ninewells Hospital Dundee (UK)

When is the study starting and how long is it expected to run for?
October 2006 to January 2010
Who is funding the study?
Diabetes UK (UK)

Who is the main contact?
Dr Miles Witham (Scientific)
m.witham@dundee.ac.uk

Contact information

Dr Miles Witham
Scientific

Section of Ageing and Health
Ninewells Hospital
Dundee
DD1 9SY
United Kingdom

Phone	+44 (0)1382 632436
Email	m.witham@dundee.ac.uk

Study information

Study design	Double blind randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Prevention
Scientific title	The effect of different doses of vitamin D(3) on markers of vascular health in patients with type 2 diabetes: a randomised controlled trial
Study objectives	To compare the effect of two different doses of vitamin D3 on vascular function in patients with type two diabetes.
Ethics approval(s)	Tayside Local Research Ethics Committee,10/09/2007, ref: 07/S1401/101
Health condition(s) or problem(s) studied	Type two diabetes mellitus
Intervention	Single dose of placebo, 100,000 units or 200,000 units of vitamin D3. Each patient will be followed-up for 16 weeks.
Intervention type	Supplement
Primary outcome measure	Change in endothelial function measured using flow-mediated dilation of the brachial artery (added 26/02/2018: at baseline, 8 and 16 weeks after vitamin D3 treatment).
Secondary outcome measures	Current secondary outcomes (as of 26/02/2018): All measures are recorded at baseline, 8 and 16 weeks after vitamin D3 treatment. 1. Office blood pressure is measured using an oscillometric system 2. Brain Natriuretic Peptide is measured from a blood sample 3. Insulin sensitivity measured using Homeostasis Model Assessment (HOMA) 4. Parathyroid Hormone (PTH) is measured from a blood sample 5. Vitamin D levels are measured using the 25 hydroxy vitamin D test 6. Calcium levels are measured from a blood sample Previous secondary outcomes: Change in: 1. Office and 24-hour Blood Pressure (BP) 2. Brain Natriuretic Peptide (BNP) 3. Heart rate variability 4. Insulin sensitivity (Homeostasis Model Assessment [HOMA]) 5. Angiotensin II, renin, aldosterone 6. Parathyroid Hormone (PTH) and 25 hydroxy vitamin D levels
Overall study start date	01/10/2006
Completion date	31/01/2010

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	Both
Target number of participants	90
Key inclusion criteria	Diagnosis of type two diabetes mellitus.
Key exclusion criteria	1. Taking vitamin D supplements 2. Serum 25 hydroxy vitamin D level of greater than 100 nmol/L 3. Serum creatinine greater than 200 umol/l 4. Liver function tests greater than three times the upper limit of normal 5. Hyper- or hypo-calcaemia (corrected calcium greater than 2.55 or less than 2.15 mmol/l, respectively) 6. Metastatic malignancy 7. Inability to give informed consent
Date of first enrolment	05/06/2008
Date of final enrolment	23/10/2009

Locations

Countries of recruitment

Scotland
United Kingdom

Study participating centre

Section of Ageing and Health

Dundee
DD1 9SY
United Kingdom

Sponsor information

University of Dundee (UK)
University/education

Research and Innovation Services
11 Perth Road
Dundee
DD1 4HN
Scotland
United Kingdom

Phone	+44 (0)1382 384664
Email	j.z.houston@dundee.ac.uk
Website	http://www.dundee.ac.uk/
"ROR"	https://ror.org/03h2bxq36

Funders

Funder type

Charity

Diabetes UK (UK) (grant ref: BDA: RD06/0003429)
Private sector organisation / Trusts, charities, foundations (both public and private)

Alternative name(s): DIABETES UK LIMITED, British Diabetic Association
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan
IPD sharing plan	The protocol is available from the authors on request but is not available online. Study data are available for non-commercial, bona-fide academic analyses in collaboration with the authors; decisions on data access will be made between the investigators and the Sponsor (University of Dundee). Participant consent for unrestricted sharing of individual participant data was not obtained Contact for data sharing: Dr Catrina Forde (c.forde@dundee.ac.uk)

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/10/2010		Yes	No
Basic results		21/02/2018	26/02/2018	No	No

Additional files

ISRCTN50587697_BasicResults_21Feb18.pdf: Uploaded 26/02/2018

Editorial Notes

26/02/2018: The following changes were made:
1. Overall trial start date was changed from 01/10/2007 to 01/10/2006.
2. Recruitment start date was changed from 01/10/2007 to 05/06/2008.
3. Recruitment end date was changed from 31/03/2009 to 23/10/2009.
4. Overall trial end date was changed from 31/03/2009 to 31/10/2010.
5. Primary and secondary outcome measures were updated.
6. Participant age group, gender, participant level data, plain english summary and basic results summary were added.