Feasibility Study of 2000 IU Per Day of Vitamin D for the Primary Prevention of Type 1 Diabetes

This study has been completed.
Sponsor:
Collaborators:
Manitoba Medical Service Foundation
Manitoba Institute of Child Health
The Health Sciences Centre Medical Staff Council
Information provided by:
Canadian Diabetes Association
ClinicalTrials.gov Identifier:
NCT00141986
First received: September 1, 2005
Last updated: April 25, 2011
Last verified: September 2005

September 1, 2005
April 25, 2011
November 2003
March 2007   (final data collection date for primary outcome measure)
change in 25(OH)D from baseline [ Time Frame: at baseline (1 month of age), 2 months of age, 6 months of age, 9 months of age, 1 year of age ] [ Designated as safety issue: Yes ]
25-hydroxyvitamin D levels
  • 25-hydroxy-vitamin D levels measured in the first year of life
  • serum and urine calcium levels
Complete list of historical versions of study NCT00141986 on ClinicalTrials.gov Archive Site
  • renal ultrasound [ Time Frame: 1 year of age ] [ Designated as safety issue: Yes ]
    to detect nephrocalcinosis
  • bone densitometry [ Time Frame: at 6 months and 1 year of age ] [ Designated as safety issue: No ]
  • diabetes autoantibody levels [ Time Frame: 1 year of age ] [ Designated as safety issue: No ]
    GADA, ICA-512, IAA
  • recruitment and retention rates [ Time Frame: 1 year of age ] [ Designated as safety issue: No ]
  • Change from baseline in serum calcium levels [ Time Frame: at baseline (1 month of age), 2 months of age, 6 months of age, 9 months of age, 1 year of age ] [ Designated as safety issue: Yes ]
  • changes in urine calcium:creatinine ratio [ Time Frame: monthly in the first year of life ] [ Designated as safety issue: Yes ]
  • renal ultrasound at 1 year of age
  • bone densitometry at 6 months and 1 year of age
  • diabetes autoantibody levels at 1 year of age
  • recruitment rates and other process outcomes
  • costs
Not Provided
Not Provided
 
Feasibility Study of 2000 IU Per Day of Vitamin D for the Primary Prevention of Type 1 Diabetes
Pilot Trial of Vitamin D for the Prevention of Type 1 Diabetes

Type 1 diabetes is a common chronic disease of childhood. It is not yet preventable. Multiple daily injections of insulin, tests of blood sugar, and careful dietary planning are required lifelong to prevent long-term complications such as blindness and kidney failure. Recent studies of potential risk factors in children with diabetes, along with studies revealing the immunologic properties of vitamin D, and experiments in animals suggest higher doses of vitamin D may prevent type 1 diabetes. For proof for human children, a randomized trial will compare groups at risk randomly assigned to receive either the usual vitamin D supplement or a higher amount, 2000 IU daily. This initial study is a small scale test of procedures.

Type 1 diabetes is a multifactorial disease with both strong genetic and non-genetic components of disease susceptibility. The uniquely strong genetic risk factor region, the human leukocyte antigen region on chromosome 6p, contributes approximately half of the genetic component and can be used for screening for diabetes risk. For example, individuals with the highest risk compound heterozygote genotype comprise 2% of the general population, but have a twenty fold increased risk for type 1 diabetes with an absolute risk of approximately 7% by age 15 years.

Studies of the non-inherited component of diabetes susceptibility implicate external environmental factors operating in the first year of life, suggesting the possibility to reverse the trend with the correct intervention. Recent data suggest that the vitamin D system is a potentially important target for therapeutic intervention to prevent type 1 diabetes. These data include epidemiological studies showing that vitamin D supplementation in infancy is associated with a substantially decreased subsequent risk of the disease, and animal work in the non-obese diabetes mouse model of autoimmune diabetes showing that the incidence of autoimmune diabetes increases when the animals are nutritionally deprived of vitamin D, and that the disease can be prevented using 1,25-dihydroxyvitamin D, and non-hypercalcemic vitamin D analogues. In vitro experiments suggest that the prevention seen in NOD mice may be due to combined effects of vitamin D on antigen presenting cells and activated T-cells.

Based on these epidemiological and animal model studies, we hypothesize that administration during infancy of cholecalciferol, the usual nutritional supplement form of vitamin D, at the increased dose of 2000 IU/day (instead of the current practice of 400 IU/day) will prevent type 1 diabetes in children from the general population at increased genetic risk.

The main objective of this proposal is to pilot a two-arm randomized controlled trial comparing these two doses. The participants are infants from the general population identified at increased genetic risk for type 1 diabetes by cord blood or filter paper blood spot HLA class II genetic screening. The study will measure key safety, compliance and pharmacokinetic, surrogate efficacy, and process outcomes including growth parameters, 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels, calcium levels in blood and urine, bone mineral content and body composition by densitometry, diabetes-related autoantibodies markers for beta-cell autoimmunity, and recruitment rates for both the screening and for the intervention trial.

Interventional
Phase 1
Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Type 1 Diabetes
  • Dietary Supplement: vitamin D3
    2000 IU per day
    Other Name: cholecalciferol
  • Dietary Supplement: vitamin D3
    400 IU per os once daily
    Other Name: Cholecalciferol
  • Experimental: Vitamin D—higher dose
    Vitamin D 2000 IU per os once daily
    Intervention: Dietary Supplement: vitamin D3
  • Active Comparator: Vitamin D—lower dose
    Vitamin D 400 IU per os once daily
    Intervention: Dietary Supplement: vitamin D3
Wicklow BA, Taback SP. Feasibility of a type 1 diabetes primary prevention trial using 2000 IU vitamin D3 in infants from the general population with increased HLA-associated risk. Ann N Y Acad Sci. 2006 Oct;1079:310-2.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
9
March 2007
March 2007   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • HLA genotypes that increase risk of type 1 diabetes: heterozygous for DRB1*03, DQA1*0501, DQB1*0201 / DRB1*04, DQA1*03011, DQB1*0302 (DRB1*04 ≠ *0403 or related alleles), or homozygous for DRB1*03, DQA1*0501, DQB1*0201, or homozygous for DRB1*04, DQA1*03011, DQB1*0302 (DRB1*04 ≠ *0403 or related alleles).

Exclusion Criteria:

  • Premature, low birthweight, or major congenital malformations or serious chronic disease
Both
up to 4 Weeks
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT00141986
1622
No
Shayne P. Taback, University of Manitoba
Canadian Diabetes Association
  • Manitoba Medical Service Foundation
  • Manitoba Institute of Child Health
  • The Health Sciences Centre Medical Staff Council
Principal Investigator: Shayne P Taback, MD FRCPC University of Manitoba
Canadian Diabetes Association
September 2005

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP