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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Dietary supplement: vitamin D3; Dietary supplement: vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • Manitoba Institute of Child Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 4 weeks (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vitamin D-higher dose; Vitamin D 2000 IU per os once daily	Dietary supplement: vitamin D3; 2000 IU per day; Other Names: cholecalciferol; Dietary supplement: vitamin D3; 400 IU per os once daily; Other Names: Cholecalciferol
ACTIVE_COMPARATOR: Vitamin D-lower dose; Vitamin D 400 IU per os once daily	Dietary supplement: vitamin D3; 2000 IU per day; Other Names: cholecalciferol; Dietary supplement: vitamin D3; 400 IU per os once daily; Other Names: Cholecalciferol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
renal ultrasound	to detect nephrocalcinosis	1 year of age
bone densitometry		at 6 months and 1 year of age
diabetes autoantibody levels	GADA, ICA-512, IAA	1 year of age
recruitment and retention rates		1 year of age
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
changes in urine calcium:creatinine ratio		monthly in the first year of life

Collaborators and Investigators

• Sponsor: Canadian Diabetes Association
• Collaborators: Manitoba Medical Service Foundation; Manitoba Institute of Child Health; The Health Sciences Centre Medical Staff Council
• Investigators: Principal Investigator: Shayne P Taback, MD FRCPC, University of Manitoba

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (ACTUAL): March 1, 2007
• Study Completion (ACTUAL): March 1, 2007

Study Registration Dates

• First Submitted: September 1, 2005
• First Submitted That Met QC Criteria: September 1, 2005
• First Posted (ESTIMATE): September 2, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): April 26, 2011
• Last Update Submitted That Met QC Criteria: April 25, 2011
• Last Verified: September 1, 2005

More Information

Terms related to this study

• Keywords: vitamin D; type 1 diabetes; prevention trial
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 1622