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

NCT ID: NCT00141986

Last Updated: 2011-04-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 9 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-11-30
• Study Completion Date: 2007-03-31

Brief 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.

Detailed 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.

Conditions

Type 1 Diabetes

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Vitamin D-higher dose

Vitamin D 2000 IU per os once daily

Group Type: EXPERIMENTAL

vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

2000 IU per day

Vitamin D-lower dose

Vitamin D 400 IU per os once daily

Group Type: ACTIVE_COMPARATOR

vitamin D3

Intervention Type: DIETARY_SUPPLEMENT

400 IU per os once daily

Interventions

vitamin D3

2000 IU per day

Intervention Type: DIETARY_SUPPLEMENT

vitamin D3

400 IU per os once daily

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

cholecalciferol; Cholecalciferol

Eligibility 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

• Maximum Eligible Age: 4 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Manitoba Medical Service Foundation

OTHER

Sponsor Role: collaborator

Manitoba Institute of Child Health

INDUSTRY

Sponsor Role: collaborator

The Health Sciences Centre Medical Staff Council

UNKNOWN

Sponsor Role: collaborator

Canadian Diabetes Association

OTHER

Sponsor Role: lead

Responsible Party

University of Manitoba

Principal Investigators

Shayne P Taback, MD FRCPC

Role: PRINCIPAL_INVESTIGATOR

University of Manitoba

Locations

Manitoba Institute of Child Health

Winnipeg, Manitoba, Canada

Countries

Canada

References

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. doi: 10.1196/annals.1375.047.

Reference Type: RESULT

PMID: 17130571 (View on PubMed)

Other Identifiers

1622

Identifier Type: -

Identifier Source: org_study_id