Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity (DIVINE)
Primary Purpose
Diabetes Mellitus Type 2, Hypovitaminosis D
Status
Unknown status
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Cholecalciferol
Orange juice
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus Type 2 focused on measuring Insulin resistance, Insulin secretory dysfunction, Inflammation, Vascular stiffness
Eligibility Criteria
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.
Sites / Locations
- Diabetes Laboratory, Oslo University Hospital AkerRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Cholecalciferol
Placebo
Arm Description
Outcomes
Primary Outcome Measures
Insulin sensitivity measured with euglycemic, hyperinsulinemic clamp
Secondary Outcome Measures
Insulin secretion measured with IVGTT
Physical activity/muscle strength
HbA1c and fasting glucose
Arterial stiffness
Differences in inflammatory markers, endothelial function and bone specific laboratory markers.
Safety of this regimen of vitamin D3 supplementation; subjects will be assessed for hypercalcemia and renal dysfunction.
Change from baseline in quality of life score between groups (SF-36).
Effect on serum lipid levels and other biochemical markers
Metabolomics analyses.
Full Information
NCT ID
NCT00992797
First Posted
October 5, 2009
Last Updated
November 2, 2009
Sponsor
University Hospital, Aker
Collaborators
University of Oslo
1. Study Identification
Unique Protocol Identification Number
NCT00992797
Brief Title
Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity
Acronym
DIVINE
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
2. Study Status
Record Verification Date
November 2009
Overall Recruitment Status
Unknown status
Study Start Date
September 2009 (undefined)
Primary Completion Date
December 2010 (Anticipated)
Study Completion Date
December 2011 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
University Hospital, Aker
Collaborators
University of Oslo
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus Type 2, Hypovitaminosis D
Keywords
Insulin resistance, Insulin secretory dysfunction, Inflammation, Vascular stiffness
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
60 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Cholecalciferol
Arm Type
Experimental
Arm Title
Placebo
Arm Type
Placebo Comparator
Intervention Type
Drug
Intervention Name(s)
Cholecalciferol
Other Intervention Name(s)
Vitamin D, ZymaD
Intervention Description
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.
Intervention Type
Other
Intervention Name(s)
Orange juice
Intervention Description
Orange juice at randomization day and at week 5.
Primary Outcome Measure Information:
Title
Insulin sensitivity measured with euglycemic, hyperinsulinemic clamp
Time Frame
Before and after the 6 months intervention period
Secondary Outcome Measure Information:
Title
Insulin secretion measured with IVGTT
Time Frame
At 0 and 6 months
Title
Physical activity/muscle strength
Time Frame
At 0 and 6 months
Title
HbA1c and fasting glucose
Time Frame
At 0, 3 and 6 months
Title
Arterial stiffness
Time Frame
At 0 and 6 months
Title
Differences in inflammatory markers, endothelial function and bone specific laboratory markers.
Time Frame
At 0, 3 and 6 months
Title
Safety of this regimen of vitamin D3 supplementation; subjects will be assessed for hypercalcemia and renal dysfunction.
Time Frame
Entire intervention period, samples taken at 0,1,3, and 6 months
Title
Change from baseline in quality of life score between groups (SF-36).
Time Frame
At 0 and 6 months
Title
Effect on serum lipid levels and other biochemical markers
Time Frame
At 0, 3 and 6 months
Title
Metabolomics analyses.
Time Frame
At 0 and 6 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Gulseth Wium, MD
Phone
4722894745
Email
diabeteslab@aus.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kåre I Birkeland, MD PhD
Organizational Affiliation
Oslo University Hospital, Aker
Official's Role
Principal Investigator
Facility Information:
Facility Name
Diabetes Laboratory, Oslo University Hospital Aker
City
Oslo
ZIP/Postal Code
0514
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
Phone
4722894745
Email
diabeteslab@aus.no
First Name & Middle Initial & Last Name & Degree
Kåre I Birkeland, MD PhD
12. IPD Sharing Statement
Citations:
PubMed Identifier
28468770
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.
Results Reference
derived
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Diabetes Intervention Trial With Vitamin D in Subjects of Nordic and Sub-Indian Ethnicity
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