Trial to Reduce IDDM in the Genetically at Risk- study

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，需要2032名符合条件的婴儿：4516名新生儿需要招募，其中45%将具有符合条件的HLA基因型（迄今为止为45.2%）。建立了一个由15个国家的73个中心组成的国际多中心联盟。到2005年1月底，我们完成了65%的招募目标，登记了3187名婴儿，随机分配了2775名，1186名符合条件的婴儿进入了干预。6-8个月的干预旨在比较水解酪蛋白和标准牛奶断奶配方奶的效果。母乳喂养的时间长短由母亲自行决定。招募和干预将在本建议继续试验的第二年完成。所有受试者在干预期间和干预后随访10年，测量完整牛奶暴露的血清学标志物、糖尿病预测性自身抗体（6岁时结束）和糖尿病的临床和/或代谢指标（10岁时结束）。一个大型的、交联的血清、DNA和冷冻保存的外周血单个核细胞储存库允许独立资助与前驱糖尿病自然史相关的辅助和机制研究和有待检验的假设。牛奶蛋白是人类最常见的完整外源断奶蛋白。如果我们的干预措施能够有效延缓自身免疫或其发展为糖尿病，这一首次T1D一级预防研究将对个人和全球社会产生深远的影响。

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(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.