The Trial to Reduce Insulin Dependent Diabetes in the Genetically at Risk ('TRIGR') will determine whether weaning to a formula in which (foreign) proteins have been extensively hydrolysed, reduces disease risk for Type 1 Diabetes (T1D) in genetically susceptible children, as it does in rodent models.
The Specific Aims are: I-a: To determine whether weaning to a hydrolysed casein formula (Nutramigen(tm)) reduces the frequency of diabetes-predictive autoantibodies, and I-b: To determine whether weaning to casein hydrolysate reduces the frequency of clinical diabetes. This double blind, randomized controlled trial in subjects with an affected first degree relative and risk-associated HLA genotypes, requires 2032 eligible infants: 4516 newborn babies need to be recruited, 45% of which will have eligible HLA genotypes (45.2% to date). An international, multicenter consortium has been developed comprising 73 centers in 15 countries. By the end of January'05 we achieved 65% of the recruitment target with 3187 infants registered, 2775 randomized and 1186 eligible infants entered into the intervention . The 6-8 month intervention is designed to compare the effects of either hydrolysed casein or standard cow milk based weaning formula. Duration of breast feeding is at the mothers' discretion. Recruitment and intervention will be completed by the second year of this proposal for trial continuation. All subjects are followed during and after the intervention period for 10 years with measurements of serological markers of intact cow milk exposure, diabetes predictive autoantibodies (the end point at age 6 years) and the clinical and/or metabolic indices of diabetes (the end point at age 10 years). A large, cross-linked repository of stored sera, DNA and cryopreserved peripheral blood mononuclear cells allows independently funded ancillary and mechanistic studies related to the natural history of prediabetes and the hypothesis to be tested. Cow milk protein is the most common intact foreign weaning protein in humans. If our intervention is effective in delaying autoimmunity or its progression to diabetes, this first ever primary prevention study of T1D will have far-reaching impact for individuals and the global society. ? ? ?

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01HD042444-07
Application #
7257251
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Grave, Gilman D
Project Start
2001-09-27
Project End
2011-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
7
Fiscal Year
2007
Total Cost
$1,557,642
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Writing Group for the TRIGR Study Group; Knip, Mikael; Ã…kerblom, Hans K et al. (2018) Effect of Hydrolyzed Infant Formula vs Conventional Formula on Risk of Type 1 Diabetes: The TRIGR Randomized Clinical Trial. JAMA 319:38-48
Nucci, Anita M; Virtanen, Suvi M; Sorkio, Susa et al. (2017) Regional differences in milk and complementary feeding patterns in infants participating in an international nutritional type 1 diabetes prevention trial. Matern Child Nutr 13:
Nucci, Anita M; Virtanen, Suvi M; Becker, Dorothy J (2015) Infant Feeding and Timing of Complementary Foods in the Development of Type 1 Diabetes. Curr Diab Rep 15:62
Knip, Mikael; Ã…kerblom, Hans K; Becker, Dorothy et al. (2014) Hydrolyzed infant formula and early ?-cell autoimmunity: a randomized clinical trial. JAMA 311:2279-87
Hadley, David; Cheung, Roy K; Becker, Dorothy J et al. (2014) Large-scale prospective T cell function assays in shipped, unfrozen blood samples: experiences from the multicenter TRIGR trial. Clin Vaccine Immunol 21:203-11
Franciscus, Margaret; Nucci, Anita; Bradley, Brenda et al. (2014) Recruitment and retention of participants for an international type 1 diabetes prevention trial: a coordinators' perspective. Clin Trials 11:150-8
Lehtonen, Eveliina; Ormisson, Anne; Nucci, Anita et al. (2014) Use of vitamin D supplements during infancy in an international feeding trial. Public Health Nutr 17:810-22
Nucci, Anita M; Becker, Dorothy J; Virtanen, Suvi M et al. (2012) Growth differences between North American and European children at risk for type 1 diabetes. Pediatr Diabetes 13:425-31
Vehik, Kendra; Cuthbertson, David; Boulware, David et al. (2012) Performance of HbA1c as an early diagnostic indicator of type 1 diabetes in children and youth. Diabetes Care 35:1821-5
Knip, Mikael; Virtanen, Suvi M; Becker, Dorothy et al. (2011) Early feeding and risk of type 1 diabetes: experiences from the Trial to Reduce Insulin-dependent diabetes mellitus in the Genetically at Risk (TRIGR). Am J Clin Nutr 94:1814S-1820S

Showing the most recent 10 out of 13 publications