E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Preventing/ delaying the onset of type 2 diabetes mellitus and cardiovascular risk factors. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 10.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10012601 |
E.1.2 | Term | Diabetes mellitus |
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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 main aim of this study is to determine whether a monthly dose of 100,000 IU of vitamin D2 or D3 (the two forms of vitamin D currently available in the market) can lead to a reduction in sugar levels (glycaemia as measured by HbA1c) in people at high risk of developing diabetes.
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E.2.2 | Secondary objectives of the trial |
To determine whether • vitamin D at the proposed dose is safe and well-tolerated by trial participants. • vitamin D2 or vitamin D3 are equally potent or whether there is a biological advantage of one over the other. • vitamin D supplementation improves risk factors associated with cardiovascular disease and strokes. • the feasibility and acceptability of high dose vitamin D supplementation to inform a future trial with diabetes and/or cardiovascular endpoints.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
4.1 Inclusion Criteria a) Number of participants: 342 (divided between Cambridge and East London, see sample size calculations in appendix) b) Age 30-75yrs. c) All ethnic groups d) People at risk of developing T2D as defined by: The Cambridge Risk Score (CRS) [80-82]. The CRS cut-offs would be 0.236 for the Black/Caribbean population, 0.127 for South Asians and 0.199 for Caucasians [83]. For other groups the cut-off for Caucasians will be used Or Impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) defined by current WHO criteria, where this information is available in medical records, or in the records of studies in which participants have consented to being re-approached to consider taking part in future studies.
Or Non-diabetic hyperglycaemia (defined as HbA1c from 5.5% to 6.49%), where this information is available in medical records, or in the records of studies in which participants have consented to being re-approached to consider taking part in future studies. e) Can provide informed consent for participation in the trial.
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E.4 | Principal exclusion criteria |
Exclusion Criteria
• Known T2D or use of oral hypoglycaemic agents (GP records, participant history) • Random blood glucose during initial screening >11 mmol/l (Screening) • Known intolerance to vitamin D2 or D3 (GP records, participant history) • Currently taking vitamin D supplements (GP records, participant history) • Prior history of hypercalcaemia (serum calcium >2.65 mmol/l) (GP records, participant history)or point of care ionised calcium >1.3mmol/l. (Screening) • Stage 4 or worse chronic kidney disease (eGFR (estimated glomerular filtration rate) < 30 ml/min) (GP records, participant history) • History of significant liver disease (AST (aspartate aminotransferase) >3 x upper limit of normal (ULN) or serum bilirubin > 2.5 x ULN) (GP records, participant history) • Past or current history of renal stones (GP records, participant history) • Known hyperparathyroidism (GP records, participant history) • Known active sarcoidosis, tuberculosis or malignancy (GP records, participant history) • Taking cardiac glycosides, thiazide diuretics or corticosteroids in the past one month (GP records, participant history) • Documented anaemia of <11g% or known haemoglobinopathy such as sickle cell anaemia and beta or alpha thalassemia (GP records, participant history) • Planned travel out of the London area or Cambridge (depending of site of recruitment) within 8 weeks of enrolment such that it will disrupt monitoring of the participant (Participant history) • Breast feeding, pregnancy or planning a pregnancy (Participant history)
NB – 1. Women of childbearing potential and men must be willing to use an effective method of contraception (hormonal or barrier method of birth control or abstinence) from the time consent is signed until 6 weeks after the end of treatment. 2. Women of childbearing potential must have a negative pregnancy test result within 7 days prior to being registered for the protocol therapy. (NOTE: Subjects are considered not of child bearing potential only if they are surgically sterile (they have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or if they are postmenopausal). 3. Women must not be breastfeeding.
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E.5 End points |
E.5.1 | Primary end point(s) |
Glycaemia as assessed by HbA1c at the final visit |
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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 | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Yes |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
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 | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | No |
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 | 2 |
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 | Information not present in EudraCT |
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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Trial will end when 342 participants have been recruited and completed the protocol. |
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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 | |
E.8.9.1 | In the Member State concerned days | |
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 |