Vidal.lshtm.ac.uk

Synopsis for Vitamin D and Longevity (VIDAL) Trial: randomised feasibility study

This is a two year randomised controlled feasibility trial on 1600 people aged 65-84 comprising two study designs:
(i) Blinded study: Participants in double-blind practices will be randomised to receive either 100,000 IU monthly (average 3300 IU/day) of oral vitamin D3 (presented as 5 ml Vigantol Oil) or double-blind placebo control (5 ml Miglyol 812 Oil) monthly for 2 years: 800 participants (ii) Open label study: Participants in unblinded practices will be randomised to receive either 100,000 IU monthly (average 3300 IU/day) of oral vitamin D3 (5 ml Vigantol Oil) monthly for 2 years or open control (no treatment): 800 participants Twenty GP practices will be cluster randomised to either blinded or open label study design. We will identify 10 pairs of GP practices matched on region and socioeconomic profile (deprivation score based on practice postcode) and randomly select one practice within each matched pair in which participants will be individually randomised between vitamin D and placebo, while participants in the other practices will be individually randomised between open-label vitamin D and open control. Primary outcomes of the feasibility study
The primary aim of the feasibility study is to establish the procedures required to conduct the main trial: our target is to
randomise 1,600 participants aged 65-84 through 20 GP practices.
Primary outcome measures:
1. The overall recruitment rate (the proportion of invited participants who are randomised) and comparison of
recruitment rate in blinded versus open control studies.
2. The overall level of compliance with study medication and comparison of blinded medication versus open label
vitamin D compliance (to evaluate whether participants taking open label vitamin D are more or less compliant than
those who are unaware of IMP status). A randomized participant is defined as compliant:
(i) If allocated to vitamin D: they report taking at least 19 (79%) of the 24 monthly doses of allocated IMP, and attend
the 2-year follow-up visit.
(ii) If allocated to no vitamin D (whether placebo or open control): they report taking a total of <300,000 IU of vitamin D
supplements over the 2 years of the study, and attend the 2-year follow-up visit. (The current UK RDA of 400 IU/day is
292,000 IU over 2 years).
These will be combined as a single outcome measure, which is the number of people we must invite to get one person
complying with allocated treatment, to demonstrate that the main trial is feasible. It equals the number invited divided
by the number randomised and compliant.
Secondary outcomes of the feasibility study
(i) The overall level of attrition (failure to attend the final 2-year visit), and a comparison of attrition between open label
and blinded practices.
(ii) Costs of blinded versus open label study designs.
(iii) Comparison of incidence of serious adverse events between vitamin D and control in blinded practices.
(iv) Comparison between vitamin D and control of numbers of infections, GP prescriptions and GP visits (a) in blinded
practices, and (b) in open-label practices. This will provide an estimate of the bias in these measures in participants
allocated to vitamin D in an open control design.
(v) Serum 25(OH)D concentration at recruitment and at 2years in relation to allocated treatment and other potential
determinants of vitamin D status (self-reported sun exposure, diet and use of vitamin D supplements).
(vi) Cause-specific mortality and cancer incidence will be ascertained by flagging in the National Health Service
Information Centre (NHS IC).
(vii) Hospital records will be collected by NHS number linkage with the Hospital Episode Statistics (HES) database.
Additional trial assessments
Before randomisation:

1) The GP nurse will record details of foreign holidays, sunbathing, sunbed use and use of vitamin supplements on the
online Case Report Form (CRF) at the GP practice with all participants before randomisation.
2) A blood sample will also be taken, and corrected serum calcium will be assayed before randomisation to establish
eligibility. Serum 25(OH)D will also be assayed. Aliquots (plasma and buffy coat) will be stored in liquid nitrogen for
further analysis (subject to additional funding) including genetic studies.

At two years:

1) All 1600 participants will attend the GP practice 2 years after randomization. A further blood sample for 25(OH)D
assay and responses to the same online CRF questions will be obtained to quantify differences in vitamin D status
and factors that may affect it between the intervention and control groups in blinded versus open label studies. 2) Summaries of GP records for all participants will also be extracted for GP visits, prescriptions and infections for one year pre-randomisation and 2 years post-randomisation. VIDAL Study Synopsis, Version 1, 22/11/2011 VIDAL Study Flowchart
Cluster randomisation within 10 matched pairs of GP practices between open randomisation with untreated controls, or double-blind randomisation with placebo control Exclusions based on review of GP records: d <65 or >84 years, no telephone, terminal illness, known active tuberculosis, referral for suspected hepatic or renal dysfunction, known sarcoidosis, hyperparathyroidism or nephrolithiasis, <3 years since remission from canc er (except non-melanoma skin cancer), taking >400 IU daily vitamin D, any other Investigational Medicinal Product (IMP) therapy within 4 months, concomitant carbamazepine, phenobarbital, phenytoin, primidone, dig oxin, oral 1-alpha-hydroxylated vitamin D preparations (e.g. alfalcalcidol, calcitriol) or the combination of a thiazide diuretic (e.g. bendrofluazide, metolazone) with a calcium supplement 18,000 potentially eligible participants aged 65-84 Send description of appropriate trial and invitation to visit practice for informed consent, blood sample and Target enrolment: 1600 (9% of eligible participants) Visit attended, signed informed consent taken, lifestyle questions completed, corrected serum calcium ≤ 2.65 Vitamin D oily solution (100,000 IU monthly) or placebo oily solution monthly for 2 years, with 3-monthly follow-up to monitor self-reported compliance and any At 24 months post-randomisation on all 1600 participants: (i) Repeat lifestyle questions and blood sample to measure serum 25-hydroxyvitamin D concentration. (ii) Flagging for lifelong follow-up through national registers for death and cancer registration, and tracing through HES (iii) GP note abstraction: GP visits, prescriptions and infections over preceding 3 years. VIDAL Study Synopsis, Version 1, 22/11/2011

Source: http://vidal.lshtm.ac.uk/files/2012/05/VIDAL-Study-Synopsis-v1-22.11.11.pdf