Trial to Reduce IDDM in the Genetically at Risk (TRIGR) Data Management Unit

描述（由申请人提供）：降低基因易感儿童胰岛素依赖型糖尿病的试验（“TRIGR”）将确定断奶配方中（外源）蛋白质被广泛水解，是否能降低基因易感儿童患1型糖尿病（T1D）的疾病风险，就像在啮齿类动物模型中一样。具体目的是：I-a：确定断奶后使用水解酪蛋白配方（Nutramigen）是否能降低糖尿病预测性自身抗体的频率；I-b：确定断奶后使用水解酪蛋白是否能降低临床糖尿病的频率。这项双盲、随机对照试验的受试者具有受影响的一级亲属和风险相关的HLA基因型，目前已进入第9个年头。建立了一个由15个国家的77个中心组成的国际多中心联盟。2160名符合条件的婴儿的登记成功完成，为所需的2032名婴儿提供了缓冲。这项为期6-8个月的干预研究于2007年完成，目的是比较水解酪蛋白和标准牛奶断奶配方奶的效果。在干预期间和干预后，对所有受试者进行了至少10年的随访，测量了完整牛奶暴露的血清学标志物、糖尿病预测自身抗体（终点为6岁）和糖尿病的临床和/或代谢指标（终点为10岁）。目前，所有计划参数均已满足，退出率< 2%，符合预期水平。一个大型的交联存储库，存储血清、DNA t细胞数据和冷冻保存的外周血单个核细胞，允许独立资助与前驱糖尿病自然史和假设相关的辅助和机制研究。该申请涵盖了数据管理部门的第11- 15年，该研究为期17年，与欧洲协调和临床中心以及美国协调和临床中心的研究一起提交。

DESCRIPTION (provided by applicant): 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") 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 is currently in its 9th year. An international, multicenter consortium has been developed comprising 77 centers in 15 countries. Enrollment of 2160 eligible infants was completed successfully, providing a cushion above the required 2032 infants. The 6-8 month intervention designed to compare the effects of either hydrolysed casein or standard cow milk based weaning formula was completed in 2007. Duration of breast feeding at the mothers' discretion was similar to or above background populations All subjects are followed during and after the intervention period for at least 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). Currently all planning parameters have been met and drop out rates are < 2% with compliance at expected levels. A large, cross-linked repository of stored sera, DNA T-cell data and 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. This application covers years 11- 15 for the Data Management Unit for this 17 year study which is submitted in tandem with those of the European coordinating and clinical centers and those of the US coordinating and clinical centers. PUBLIC HEALTH RELEVANCE: Cow milk protein is the most common intact foreign weaning protein in humans. If our intervention is effective in delaying autoimmunity or ultimately its progression to clinical diabetes, this first ever primary prevention study of T1D, will have far-reaching impact for individuals and the global society.