Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity

Study Overview
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Brief Summary
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The aim of this 6 months study is to evaluate the metabolic effects of 400.000-600.000 IU of vitamin D supplementation in subjects with type 2 diabetes and hypovitaminosis D. The main hypothesis is that subjects with low levels of 25-OH-vitamin D will benefit from supplementation with cholecalciferol in sufficient doses to optimize serum levels.

Detailed Description
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Accumulating evidence suggests that hypovitaminosis D may be associated with the development of type 2 diabetes and disturbances in glucose and insulin metabolism. There is lack of data from randomized, controlled studies of sufficient duration and with the use of sufficient doses of vitamin D to assess the importance of vitamin D supplementation in glucose metabolism in type 2 diabetes.

Official Title
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A Randomized Controlled Trial of the Effect of Vitamin D Supplementation on Insulin Sensitivity and Secretion in Subjects With Type 2 Diabetes of Nordic and Sub-Indian Ethnicity .

Conditions
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Diabetes Mellitus Type 2, Hypovitaminosis D

Intervention / Treatment
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* Drug: Cholecalciferol
* Other: Orange juice


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Moderate (S-25OHD 25-50 nmol/l) to severe (S-25OHD < 25 nmol/l) vitamin D deficiency measured at Visit 1. Patients with type 2 diabetes, including drug naïve subjects, subjects using oral anti-diabetic medication and subjects on insulin treatment. All medication must be in stable doses during the 4 week lead-in period. HbA1c < 11 % at Visit 1. Able to communicate in Norwegian. Men and women ≥ 18 years. Norwegian or South Asian ethnicity. Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study. All WOCBP must have negative serum or urine pregnancy test at enrollment, randomization, titration visit and final study assessment. Antihypertensive medication, lipid lowering drugs, oral contraceptives, hormone replacement therapy, multivitamin supplements and nutritional supplements are allowed if the subjects adhere to the same regimen during the study Exclusion Criteria: Subjects not having type 2 diabetes. SBP ≥ 160 or DBP ≥ 95 at Visit 1. Significant renal disease or chronic renal impairment, GFR< 30 ml/min. Significant liver disease or ASAT or ALAT >3x UNL. Malignancy during the last five years. Hypercalcemia at Visit 1. A history of kidney stone disease WOCBP unwilling or unable to use an acceptable method to avoid pregnancy. Pregnant or breastfeeding women. Chronic inflammatory disease in active phase Long term (>2 weeks) use of corticosteroids last 3 months Mental condition (psychiatric or organic cerebral disease) rendering the subject unable to understand the nature, scope and possible consequences of the study. Drug or alcohol abuse. BMI > 45 kg/m2 or bariatric surgery (<5 years). Anemia Cardiovascular disease (myocardial infarction, unstable angina pectoris or stroke) during the last 6 months. Any medical condition that in the judgment of the investigator would jeopardize the subject's safety or evaluation of the study drug for efficacy and safety.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholecalciferol<br> | Drug: Cholecalciferol<br>* Cholecalciferol 200.000 IU pr ampoule, 400.000 IU given at randomization day, followed by additionally 200.000 IU at week 5 if serum 25(OH)D < 100 nmol/L. If serum 25(OH)D > 100 placebo will be given. The cholecalciferol will be given in orange juice.<br>* Other names: ZymaD;|
| Placebo Comparator: Placebo<br> | Other: Orange juice<br>* Orange juice at randomization day and at week 5.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sensitivity measured with euglycemic, hyperinsulinemic clamp |  | Before and after the 6 months intervention period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin secretion measured with IVGTT |  | At 0 and 6 months | 
| Physical activity/muscle strength |  | At 0 and 6 months | 
| HbA1c and fasting glucose |  | At 0, 3 and 6 months | 
| Arterial stiffness |  | At 0 and 6 months | 
| Differences in inflammatory markers, endothelial function and bone specific laboratory markers. |  | At 0, 3 and 6 months | 
| Safety of this regimen of vitamin D3 supplementation; subjects will be assessed for hypercalcemia and renal dysfunction. |  | Entire intervention period, samples taken at 0,1,3, and 6 months | 
| Change from baseline in quality of life score between groups (SF-36). |  | At 0 and 6 months | 
| Effect on serum lipid levels and other biochemical markers |  | At 0, 3 and 6 months | 
| Metabolomics analyses. |  | At 0 and 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Insulin resistance, Insulin secretory dysfunction, Inflammation, Vascular stiffness