E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The aim of vitamin D supplementation is to increase circulating 25(OH) vitamin D level in the general population. The aim of the main trial for which this is a feasibility study is to determine whether this will improve general health, which is uncertain. |
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E.1.1.1 | Medical condition in easily understood language |
The main aim of the larger randomised trial for which this is a feasibility study is to discover whether vitamin D supplementation prolongs life in healthy men and women aged 65-84. |
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MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The principal aim of the feasibility study is to establish the procedures required to conduct the main trial. We shall determine the recruitment rate and the compliance rate (the proportion adhering to allocated treatment over 2 years) in practices with placebo control, and in practices with open control. We shall also determine contamination rates (self-administration of >400 IU vitamin D per day or equivalent) in those allocated placebo and those allocated to open control. IMP adherence and use of additional vitamin D supplements will be studied both by self-report and from blood levels of 25(OH) vitamin D at entry and at 2 years. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives (i) To compare costs of placebo and open control designs, and hence to determine whether the extra costs of placebo control would be justified in the main trial. (ii) To provide unbiased data on the incidence of adverse events (vitamin D v. placebo control). (iii) To provide unbiased data on infections, prescriptions and frequency of GP visits (vitamin D v. placebo control), and to estimate the bias in these measures in participants allocated to vitamin D in an open control design. (iv) To analyse circulating 25(OH)D at recruitment and at 2-year follow-up in relation to allocation and potential determinants of vitamin D status, particularly self-reported sun exposure. (v) To establish the feasibility of flagging for lifelong follow-up through national registers for death and cancer registration, and tracing through the Hospital Episodes Statistics database (HES) for hospital admissions and diagnoses. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
• Age ≥ 65 years and ≤ 84 years at enrolment • Contactable by telephone, able to receive postal recorded deliveries, and able to attend enrolment at the GP surgery • GP notes for the previous year are available |
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E.4 | Principal exclusion criteria |
• Known active tuberculosis, sarcoidosis, hyperparathyroidism, past or present nephrolithiasis, vitamin D intolerance, referral for suspected hepatic or renal dysfunction, terminal illness, any malignancy other than non-melanoma skin cancer not in remission for ≥ 3 years • Planning to move from the GP practice or to emigrate within 5 years • Any other condition that in the PI’s or CI’s judgement might compromise participant safety or compliance, interfere with evaluation or preclude completion of the study. • Baseline corrected serum calcium > 2.65 mmol/L • Taking dietary supplement or other medication containing >400 IU (10 micrograms) per day vitamin D • Treatment with any other investigational medical product or device up to 4 months before first dose of IMP • Concomitant therapy with any of the following: carbamazepine, phenobarbital, phenytoin, primidone, digoxin, 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 |
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E.5 End points |
E.5.1 | Primary end point(s) |
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 recruitment rate (the proportion of invited potential participants who are randomised). 2. The overall compliance rate. 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. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The recruitment rate will be monitored continuously during the first year. Recruitment should be completed after 1 year. Other outcome measures will be analysed when all patients have completed the 2 years of treatment, i.e. at 3 years. |
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E.5.2 | Secondary end point(s) |
Secondary objectives (i) To compare costs of placebo and open control designs, and hence to determine whether the extra costs of placebo control would be justified in the main trial. (ii) To provide unbiased data on the incidence of adverse events (vitamin D v. placebo control). (iii) To provide unbiased data on infections, prescriptions and frequency of GP visits (vitamin D v. placebo control), and to estimate the bias in these measures in participants allocated to vitamin D in an open control design. (iv) To analyse circulating 25(OH)D at recruitment and at 2-year follow-up in relation to allocation and potential determinants of vitamin D status, particularly self-reported sun exposure. (v) To establish the feasibility of flagging for lifelong follow-up through national registers for death and cancer registration, and tracing through the Hospital Episodes Statistics database (HES) for hospital admissions and diagnoses. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
All secondary endpoints will be analysed when all participants have completed the 2 years of treatment, i.e. at 3 years. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Feasibility study. The main outcome is the proportion of those invited who enrol. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Randomisation of GP practices to open or double blind. Individual randomisation to IMP/no IMP. |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |