Clinical trial NCT00992797: Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity
Official title: 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 .
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Diabetes Mellitus Type 2
Hypovitaminosis D
Keywords: Insulin resistance
Insulin secretory dysfunction
Inflammation
Vascular stiffness
Lead sponsor: University Hospital, Aker
Sponsor class: OTHER
Collaborators: name: University of Oslo
First posted: 2009-10-09
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion criteria:

1. Moderate (S-25OHD 25-50 nmol/l) to severe (S-25OHD \< 25 nmol/l) vitamin D deficiency measured at Visit 1.
2. 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.
3. HbA1c \< 11 % at Visit 1.
4. Able to communicate in Norwegian.
5. Men and women ≥ 18 years.
6. Norwegian or South Asian ethnicity.
7. 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.
8. 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:

1. Subjects not having type 2 diabetes.
2. SBP ≥ 160 or DBP ≥ 95 at Visit 1.
3. Significant renal disease or chronic renal impairment, GFR\< 30 ml/min.
4. Significant liver disease or ASAT or ALAT \>3x UNL.
5. Malignancy during the last five years.
6. Hypercalcemia at Visit 1.
7. A history of kidney stone disease
8. WOCBP unwilling or unable to use an acceptable method to avoid pregnancy.
9. Pregnant or breastfeeding women.
10. Chronic inflammatory disease in active phase
11. Long term (\>2 weeks) use of corticosteroids last 3 months
12. Mental condition (psychiatric or organic cerebral disease) rendering the subject unable to understand the nature, scope and possible consequences of the study.
13. Drug or alcohol abuse.
14. BMI \> 45 kg/m2 or bariatric surgery (\<5 years).
15. Anemia
16. Cardiovascular disease (myocardial infarction, unstable angina pectoris or stroke) during the last 6 months.
17. 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.

Primary outcomes:
measure: Insulin sensitivity measured with euglycemic, hyperinsulinemic clamp
timeFrame: Before and after the 6 months intervention period
Secondary outcomes:
measure: Insulin secretion measured with IVGTT
timeFrame: At 0 and 6 months
measure: Physical activity/muscle strength
timeFrame: At 0 and 6 months
measure: HbA1c and fasting glucose
timeFrame: At 0, 3 and 6 months
measure: Arterial stiffness
timeFrame: At 0 and 6 months
measure: Differences in inflammatory markers, endothelial function and bone specific laboratory markers.
timeFrame: At 0, 3 and 6 months
measure: Safety of this regimen of vitamin D3 supplementation; subjects will be assessed for hypercalcemia and renal dysfunction.
timeFrame: Entire intervention period, samples taken at 0,1,3, and 6 months
measure: Change from baseline in quality of life score between groups (SF-36).
timeFrame: At 0 and 6 months
measure: Effect on serum lipid levels and other biochemical markers
timeFrame: At 0, 3 and 6 months
measure: Metabolomics analyses.
timeFrame: At 0 and 6 months
Other outcomes:
Locations:
city: Oslo
country: Norway
facility: Diabetes Laboratory, Oslo University Hospital Aker
Study officials:
affiliation: Oslo University Hospital, Aker
name: Kåre I Birkeland, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gulseth HL, Wium C, Angel K, Eriksen EF, Birkeland KI. Effects of Vitamin D Supplementation on Insulin Sensitivity and Insulin Secretion in Subjects With Type 2 Diabetes and Vitamin D Deficiency: A Randomized Controlled Trial. Diabetes Care. 2017 Jul;40(7):872-878. doi: 10.2337/dc16-2302. Epub 2017 May 3.