Trial to Reduce IDDM in the Genetically at Risk -study

描述（由申请人提供）：摘要在遗传风险人群中减少胰岛素依赖型糖尿病的试验（“TRIGR”）将确定断奶至（外源）蛋白质已被广泛水解的配方食品是否会降低遗传易感儿童中1型糖尿病（T1 D）的疾病风险，就像在啮齿动物模型中一样。具体目标是：I-a：确定断奶至水解酪蛋白配方（Nutramigen）是否降低糖尿病预测性自身抗体的频率，和I-b：确定断奶至酪蛋白水解物是否降低临床糖尿病的频率。这项双盲、随机对照试验在具有受影响的一级亲属和风险相关HLA基因型的受试者中进行，目前已进入第9年。已经建立了一个国际多中心联盟，由15个国家的77个中心组成。成功完成了2160名合格婴儿的入组，为所需的2032名婴儿提供了缓冲。2007年完成了旨在比较水解酪蛋白或标准牛乳断奶配方奶粉效果的6-8个月干预。在干预期期间和之后对所有受试者进行至少10年的随访，测量完整牛乳暴露的血清学标志物、糖尿病预测性自身抗体（终点在6岁）和糖尿病的临床和/或代谢指数（终点在10岁）。目前，所有规划参数都已达到，辍学率< 2%，符合预期水平。储存血清、DNA、T细胞数据和冷冻保存的外周血单核细胞的大型交联储存库允许独立资助的与前驱糖尿病的自然史和待检验的假设相关的辅助和机制研究。本申请涵盖了赫尔辛基大学国际协调中心和核心自身抗体实验室以及欧洲和澳大利亚研究中心的11-15年研究，该研究将与美国协调中心和临床中心以及数据管理部门的研究同时提交。

DESCRIPTION (provided by applicant): Abstract 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 hydrolyzed 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 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 International Coordinating Center and the Core Autoantibody Laboratory at the University of Helsinki and for the study centers in Europe and Australia for this 17 year study which is submitted in tandem with those of the US coordinating center and clinical centers and that of the Data Management Unit.