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.

Condition	Intervention	Phase
Type 1 Diabetes	Drug: vitamin D3 (cholecalciferol) 2000 IU per day	Phase I

Further Study Details: 

Primary Outcomes: 25-hydroxy-vitamin D levels measured in the first year of life; serum and urine calcium levels
Secondary Outcomes: 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
Expected Total Enrollment:  20

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.

Ages Eligible for Study:  up to  4 Weeks,  Genders Eligible for Study:  Both

Criteria

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

Please refer to this study by ClinicalTrials.gov identifier  NCT00141986

Dan Catte, RD      977-5645    dcatte@mich.ca
Lori D Berard, RN      204-789-3228    lberard@hsc.mb.ca

Canada, Manitoba
      Manitoba Institute of Child Health, Winnipeg,  Manitoba,  Canada; Recruiting

Study chairs or principal investigators

Shayne P Taback, MD FRCPC,  Principal Investigator,  University of Manitoba   

Study ID Numbers:  1622
Last Updated:  September 1, 2005
Record first received:  September 1, 2005
ClinicalTrials.gov Identifier:  NCT00141986
Health Authority: Canada: Health Canada
ClinicalTrials.gov processed this record on 2005-09-06