Vitamin D supplement on morbidity and mortality Nutritional, Metabolic, Endocrine Sequelae of external causes of morbidity and mortality
Conditions
Interventions
Participants will receive either:
1. 100,000 IU monthly (average 3300 IU/day) of oral vitamin D3 or double-blind placebo control (800 participants)
2. 100,000 IU monthl
Sponsors
London School of Hygiene & Tropical Medicine (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged between 65 and 84 years at enrolment 2. Contactable by telephone, able to attend enrolment at the GP surgery, and able to give informed consent 3. Baseline corrected serum calcium 2.65 mmol/L 4. Registered with one of the 20 participating GP practices
Exclusion criteria
Exclusion criteria: 1. Aged 84 years 2. No telephone 3. Terminal illness 4. Known active tuberculosis 5. Referral for suspected hepatic or renal dysfunction 6. Known sarcoidosis, hyperparathyroidism or nephrolithiasis 7. 400mg daily vitamin D 9. Any other Investigational Medicinal Product (IMP) therapy within 4 months 10. Concomitant carbamazepine, phenobarbital, phenytoin, primidone, 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. The successful establishment of the procedures required to identify, invite and recruit eligible patients. Our target is to randomise 1,600 participants aged 65-84 through 20 GP practices. 2. Overall recruitment rate and comparison of recruitment rate in placebo versus open control studies 3. Overall level of compliance with study medication and comparison of placebo versus open control medication compliance (to evaluate whether participants taking open label vitamin D are more or less compliant than those who are unaware of IMP status) 4. Contamination: whether open controls are more likely to take vitamin D supplements than placebo controls 5. Overall level of attrition over 2 years and comparison of attrition rates in open label and placebo-controlled practices 6. Costs of placebo versus open control study designs to determine whether the extra costs of placebo would be justified in the main trial (participants randomised to an open untreated control arm may take supplements containing vitamin D more frequently than those on placebo) 7. Comparison of incidence of serious adverse events between vitamin D and control in placebo-controlled practices 8. Comparison between vitamin D and control of infections, GP prescriptions and frequency of GP visits: 8.1. In placebo-controlled practices, and 8.2. 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 9. Serum 25(OH)D concentration at recruitment and at 2-year follow-up in relation to potential determinants of vitamin D status including self-reported compliance with study medication 10. Cause-specific mortality and cancer incidence will be ascertained by flagging in the National Health Service Information Centre (NHS IC) | — |
Secondary
| Measure | Time frame |
|---|---|
| Before randomisation: 1. An online lifestyle questionnaire on foreign holidays, sunbathing, sunbed use and use of vitamin supplements will be completed at the GP practice by all participants (treated and control) 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 a second copy of the same online questionnaire will be obtained to quantify differences in vitamin D status 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. | — |
Countries
United Kingdom
Outcome results
None listed