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

 描述（由申请方提供）：在遗传风险人群中减少胰岛素依赖型糖尿病（TRIGR）试验的完成将确定断奶至（外源）蛋白质已被广泛水解的配方食品是否能降低遗传易感儿童患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：确定停用酪蛋白水解物是否可降低临床糖尿病的发生率;以及I-b：评估水解研究配方食品治疗组中自身抗体和T1 D的年龄校正发生率（非累积发生率）向后期的潜在变化。这项在受影响的一级亲属和风险相关HLA基因型受试者中进行的时间最长和规模最大的双盲随机对照试验目前已进入第14个年头。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2159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。母乳喂养的持续时间由母亲自行决定，与背景人群相似或高于背景人群。在干预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免疫标志物、糖尿病预测性自身抗体和糖尿病的临床和/或代谢指数（终点为10-14岁）。目前，所有规划参数均已达到，辍学率为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16- 18年，与美国协调中心和临床中心以及数据管理部门的申请同时提交。要求提供资金以完成审判和报告结果。

 DESCRIPTION (provided by applicant): The completion of 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 hydrolyzed, 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 casein hydrolysate reduces the frequency of clinical diabetes; and I-b: To assess a potential shift in the age-adjusted incidence (not the cumulative incidence) of autoantibodies and T1D to a later time period in the group treated with the hydrolyzed study formula. This longest and largest, double-blind, randomized controlled trial in subjects with an affected first-degree relative and risk-associated HLA genotypes is currently in its 14th year. An international, multicenter consortium has been developed comprising 77 centers in 15 countries. Enrollment of 2159 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 was at the mothers' discretion and similar to or above background populations. All subjects are followed during and after the intervention period for at least 10 years with measurements of immune markers of intact cow milk exposure, diabetes predictive autoantibodies and the clinical and/or metabolic indices of diabetes (the end point at age 10-14 years). Currently all planning parameters have been met and drop- out rate is 2% with compliance at expected level. 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 16- 18 for the International Coordinating Center and the Core Autoantibody Laboratory at the University of Helsinki and for the study centers in Europe and Australia which is submitted in tandem with those of the US coordinating center and clinical centers and that of the Data Management Unit. Funding is requested for completing the trial and reporting the outcome.