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

在遗传风险 (TRIGR) 数据管理单元中进行减少 IDDM 的试验

• 批准号: 8486297
• 负责人: JEFFREY P KRISCHER
• 金额: $ 72.45万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-10 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8486297
• 关键词: 10 year old; 6 year old; Address; Adherence; Adverse event; Affect; Ancillary Study; Antibodies; Autoantibodies; Autoimmunity; Breast Feeding; Caseins; Cattle; Child; Clinical; Clinical Trials Data Monitoring Committees; Control Groups; Country; DNA; Data; Development; Diabetes Mellitus; Diabetes prevention; Dietary Proteins; Double-Blind Method; Drops; Early Diagnosis; Electronics; Enrollment; European; Exposure to; Extravasation; Family; First Degree Relative; Frequencies; Funding; Genotype; Human; Immunity; Incidence; Individual; Infant; Infant formula; Infection; Insulin-Dependent Diabetes Mellitus; International; Intervention; Intestines; Life; Measurement; Measures; Medical; Metabolic; Milk; Milk Proteins; Monitor; Mothers; Natural History; Nutrient; Nutritional; Online Systems; Patient Care; Peripheral Blood Mononuclear Cell; Pilot Projects; Population; Prediabetes syndrome; Primary Prevention; Proteins; Protocols documentation; Quality Control; Randomized Controlled Trials; Relative Risks; Reporting; Research Design; Risk; Risk Factors; Rodent; Rodent Model; Role; Safety; Self Tolerance; Serum; Societies; System; T cell response; T-Lymphocyte; Testing; Weaning; base; casein hydrolysate; clinical research site; cost; crosslink; data management; diabetes mellitus genetics; diabetes risk; disorder risk; indexing; infancy; islet; meetings; prevent; protein complex; repository; serological marker; therapy design

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.

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“)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的人类白细胞抗原基因型别受试者的双盲随机对照试验目前已进入第9个年头。已经建立了一个由15个国家的77个中心组成的国际多中心财团。2160名符合条件的婴儿顺利完成入学，为所需的2032名婴儿提供了缓冲。这项为期6-8个月的干预计划于2007年完成，旨在比较酪蛋白水解物或标准牛奶断奶配方的效果。由母亲自行决定的母乳喂养持续时间与背景人口相似或高于背景人口所有受试者在干预期内及之后被跟踪至少10年，测量完整牛奶暴露的血清标志物、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)。目前，所有计划参数都已达到，辍学率为&lt；2%，符合预期水平。储存的血清、DNA T细胞数据和冷冻保存的外周血单核细胞的大型交叉链接库使独立资助的与糖尿病前期自然病史和假说相关的辅助和机制研究得以检验。这份申请涵盖了数据管理单位在这项17年研究中的第11-15年，这项研究是与欧洲协调和临床中心以及美国协调和临床中心的数据一起提交的。