Trial to Reduce IDDM in the Genetically at Risk- study

描述(由申请人提供)：降低处于遗传风险中的胰岛素依赖型糖尿病的试验(TRIGR)将确定断奶后服用一种(外来)蛋白质已被广泛水解的配方奶，是否像在啮齿动物模型中那样，降低遗传易感儿童患1型糖尿病(T1D)的疾病风险。具体目标是：i-a：确定停用酪蛋白水解物(Nutramilen(Tm))是否会降低糖尿病预测自身抗体的频率，i-b：确定停用酪蛋白水解物是否会降低临床糖尿病的频率。这项针对受影响的一级亲属和风险相关基因的受试者进行的双盲随机对照试验，需要2032名符合条件的婴儿：需要招募4516名新生儿，其中45%将具有符合条件的人类白细胞抗原(45.2%)基因。已经建立了一个由15个国家的73个中心组成的国际多中心财团。截至2005年1月底，我们完成了招募目标的65%，3187名登记在册的婴儿，2775名随机进入干预的婴儿，1186名符合条件的婴儿进入干预。6-8个月的干预旨在比较以酪蛋白水解物和标准牛奶为基础的断奶配方的效果。母乳喂养的持续时间由母亲自行决定。征聘和干预工作将在本提议的第二年前完成，以便继续进行试验。所有受试者在干预期间和干预后进行为期10年的跟踪，测量接触完整牛奶的血清学标志物、糖尿病预测自身抗体(6岁结束时)和糖尿病的临床和/或代谢指标(10岁结束时)。储存的血清、DNA和冷冻保存的外周血单核细胞的大型、交叉链接的储存库允许独立资助的与糖尿病前期的自然病史和假说相关的辅助和机制研究。牛奶蛋白是人类最常见的完整的异种断奶蛋白。如果我们的干预措施在延缓自身免疫或其进展为糖尿病方面有效，这项首次针对T1D的初级预防研究将对个人和全球社会产生深远影响。

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.