E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Impaired glucose tolerance, impaired fasting glucose and type 2 diabetes mellitus. Vitamin D deficiency. |
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E.1.1.1 | Medical condition in easily understood language |
Pre-diabetes and type 2 diabetes. Vitamin D deficiency. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10018429 |
E.1.2 | Term | Glucose tolerance impaired |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10056997 |
E.1.2 | Term | Impaired fasting glucose |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10067585 |
E.1.2 | Term | Type 2 diabetes mellitus |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047626 |
E.1.2 | Term | Vitamin D deficiency |
E.1.2 | System Organ Class | 10027433 - Metabolism and nutrition disorders |
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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 |
To evaluate, in patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), IFG+IGT or diet treated type 2 diabetes and vitamin D deficiency, the impact on beta cell function of vitamin D3 treatment. |
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E.2.2 | Secondary objectives of the trial |
To evaluate, in patients with IFG, IGT, IFG+IGT or diet treated type 2 diabetes and vitamin D deficiency, the impact of vitamin D3 treatment on:
Change in insulin sensitivity assessed as the ratio of the glucose infusion rate and plasma insulin concentration (M/I) during hyperglycemic clamp.
Change in glucose tolerance assessed by an oral glucose tolerance test (OGTT).
Change in fasting plasma glucose and HbA1c.
Change in CVD risk markers/lipids.
Change in hormones as leptin, adiponectin and GLP-1.
Change in 25-OH-vitamin D and PTH.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Informed consent obtained before any trial-related activities.
2. Meeting criteria for IFG, IGT, IFG+IGT or diabetes mellitus at screening.
3. Age 45 - 75 years, female or male.
4. BMI ≤ 32 kg/m2.
5. HbA1c ≤ 7.0 % (MonoS) or ≤ 63 mmol/mol (IFCC) at screening.
6. 25-OH-Vitamin D < 75 nmol/l
7. Able and willing to perform tests and examinations specified in the protocol.
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E.4 | Principal exclusion criteria |
1. Previous participation in this trial. Participation is defined as randomization.
2. Anticipated change in dose of concomitant medication which may interfere with glucose metabolism, such as systemic corticosteroids, non-selective beta-blockers, mono amine oxidase (MAO) inhibitors and anabolic steroids.
3. Treatment with any vitamin D preparation.
4. Regular sun-bathing.
5. Sun-bathing in a southern country for ≥ 1 week within the last 3 months.
6. Hypercalcemia at screening.
7. Hypervitamninosis D at screening.
8. Hyperphosphatemia at screening.
9. Sarcoidosis or other granulomatous disease.
10. Treatment with phenytoin, barbiturates, rifampicin, isoniazid, cardiac glycosides, orlistat or colestyramin.
11. Impaired hepatic function defined as alanine aminotransferase (ALAT) >= three times the upper reference limit.
12. Impaired renal function defined as S-creatinine >133 µmol/L for males and >115 µmol/L for females.
13. Cardiac disease defined as:
a. Unstable angina pectoris
b. Myocardial infarction within the last 6 months
c. Congestive heart failure NYHA class III and IV
14. Cerebral stroke within the last 6 months.
15. Uncontrolled treated/untreated hypertension (systolic blood pressure >= 180 mmHg and/or diastolic blood pressure >= 110mmHg).
16. Known or suspected allergy to trial product or any contraindications to trial product.
17. Cancer (except basal cell skin cancer or squamous cell skin cancer).
18. Anti-diabetic medication of any kind.
19. Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods.
20. Known or suspected abuse of alcohol or narcotics.
21. Mental incapacity, unwillingness or language barrier precluding adequate understanding or co-operation.
22. Any other condition that the Investigator and/or Sponsor feel would interfere with trial participation or evaluation of results.
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E.5 End points |
E.5.1 | Primary end point(s) |
Placebo-controlled change in beta cell function from baseline after 8 weeks. The plasma insulin response (I) during hyperglycemic clamp will assess beta cell function. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Change from the baseline investigation to the end-of-study investigation after 8 weeks of treatment. |
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E.5.2 | Secondary end point(s) |
Placebo-controlled change from baseline after 8 weeks in:
Change in insulin sensitivity assessed as the ratio of the glucose infusion rate and plasma insulin concentration (M/I) during hyperglycemic clamp.
Change in glucose tolerance assessed by an oral glucose tolerance test (OGTT).
Change in fasting plasma glucose and HbA1c.
Change in CVD risk markers/lipids.
Change in hormones as leptin, adiponectin and GLP-1.
Change in 25-OH-vitamin D and PTH. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Change from the baseline investigation to the end-of-study investigation after 8 weeks of treatment. |
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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 | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | No |
E.6.5 | Efficacy | Yes |
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 | No |
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 | 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.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
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 | No |
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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Last visit of the last subject, planned to Q3 2012. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | 0 |