Study design of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR).

The hypothesis for this study is that weaning to an extensively hydrolyzed infant formula will decrease the incidence of type 1 diabetes (T1D), as it does in all relevant animal models for the disease. This will be tested in children who carry risk-associated human leukocyte antigen genotypes and have a first-degree relative with T1D. The trial will use a double-blind, prospective, placebo-controlled intervention protocol, comparing casein hydrolysate with a conventional cow's milk (CM)-based formula. A secondary aim is to determine relationships between CM antibodies, a measure of CM exposure, and diabetes-associated autoantibodies. To achieve an 80% power for the detection of a 40% intervention-induced difference in the development of autoantibodies and subsequent diabetes, the study requires 2032 subjects. A multicenter, international, collaborative effort is necessary to achieve recruitment targets. A collaborative international study group of 78 clinical centers in 15 countries has therefore been assembled for this purpose.