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

Type 1 Diabetes Clinical Trial

Official title:

Pilot Trial of Vitamin D for the Prevention of Type 1 Diabetes

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00141986
• Other study ID #: 1622
• Status: Completed
• Phase: Phase 1
• First received: September 1, 2005
• Last updated: April 25, 2011
• Start date: November 2003
• Est. completion date: March 2007

Study information

• Verified date: September 2005
• Source: Canadian Diabetes Association
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Health Canada
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 9
• Est. completion date: March 2007
• Est. primary completion date: March 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 4 Weeks

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

Dietary Supplement:
• vitamin D3
2000 IU per day
• vitamin D3
400 IU per os once daily

Locations

Country	Name	City	State
Canada	Manitoba Institute of Child Health	Winnipeg	Manitoba

Sponsors (4)

Lead Sponsor	Collaborator
Canadian Diabetes Association	Manitoba Institute of Child Health, Manitoba Medical Service Foundation, The Health Sciences Centre Medical Staff Council

Country where clinical trial is conducted

Canada, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	change in 25(OH)D from baseline	25-hydroxyvitamin D levels	at baseline (1 month of age), 2 months of age, 6 months of age, 9 months of age, 1 year of age	Yes
Secondary	renal ultrasound	to detect nephrocalcinosis	1 year of age	Yes
Secondary	bone densitometry		at 6 months and 1 year of age	No
Secondary	diabetes autoantibody levels	GADA, ICA-512, IAA	1 year of age	No
Secondary	recruitment and retention rates		1 year of age	No
Secondary	Change from baseline in serum calcium levels		at baseline (1 month of age), 2 months of age, 6 months of age, 9 months of age, 1 year of age	Yes
Secondary	changes in urine calcium:creatinine ratio		monthly in the first year of life	Yes