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

This study is currently recruiting patients.
Verified by Canadian Diabetes Association September 2005

Sponsors and Collaborators: Canadian Diabetes Association
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

Purpose
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

MedlinePlus related topics: Diabetes Type 1

Study Type: Interventional
Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety Study
Official Title: Pilot Trial of Vitamin D for the Prevention of Type 1 Diabetes
Further study details as provided by Canadian Diabetes Association: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 Study start: November 2003; Expected completion: September 2007

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.
Eligibility
Ages Eligible for Study: up to 4 Weeks, Genders Eligible for Study: Both CriteriaInclusion 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
Location and Contact Information
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
Daniel Catte dcatte@mich.ca
Lori Berard lberard@hsc.mb.ca
Shayne P Taback, MD FRCPC, Principal Investigator
Hope A Weiler, PhD, Sub-Investigator
Cheryl Rockman-Greenberg, MD FRCPC, Sub-Investigator
Heather J Dean, MD FRCPC, Sub-Investigator
Tom Blydt-Hansen, MD FRCPC, Sub-Investigator

Study chairs or principal investigators
Shayne P Taback, MD FRCPC, Principal Investigator, University of Manitoba More Information
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 2007-01-12
U.S. National Library of Medicine, Contact NLM Customer Service
National Institutes of Health, Department of Health & Human Services
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