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: 8040224
• 负责人: JEFFREY P KRISCHER
• 金额: $ 74.59万
• 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/8040224
• 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. PUBLIC HEALTH RELEVANCE: Cow milk protein is the most common intact foreign weaning protein in humans. If our intervention is effective in delaying autoimmunity or ultimately its progression to clinical diabetes, this first ever primary prevention study of T1D, will have far-reaching impact for individuals and the global society.

描述（由申请人提供）：减少遗传风险中胰岛素依赖性糖尿病的试验（“TRIGR”）将确定断奶后使用（外来）蛋白质已被广泛水解的配方奶粉是否可以降低遗传易感儿童患 1 型糖尿病（T1D）的疾病风险，就像在啮齿动物模型中所做的那样。具体目标是： I-a：确定断奶使用水解酪蛋白配方奶粉（Nutramigen”）是否会降低糖尿病预测自身抗体的发生率，I-b：确定断奶使用酪蛋白水解物是否会降低临床糖尿病的发生率。这项双盲、随机对照试验的对象是具有受影响的一级亲属和风险相关 HLA 基因型的受试者。 目前已进入第九个年头。一个由 15 个国家的 77 个中心组成的国际多中心联盟已经成立。 2160 名符合条件的婴儿已成功完成注册，为所需的 2032 名婴儿提供了缓冲。旨在比较水解酪蛋白或标准牛奶断奶配方奶粉效果的 6-8 个月干预措施于 2007 年完成。由母亲自行决定的母乳喂养持续时间相似 在干预期间和之后对所有受试者进行至少 10 年的跟踪，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（终点为 6 岁）以及糖尿病的临床和/或代谢指数（终点为 10 岁）。目前，所有计划参数均已满足，退出率 < 2%，符合预期水平。一个大的、 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交联存储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以及待测试的假设。该申请涵盖了这项为期 17 年的研究的数据管理单元的 11-15 年，该申请与欧洲协调和临床中心以及美国协调和临床中心的申请同时提交。 临床中心。 公众健康相关性：牛奶蛋白是人类最常见的完整外来断奶蛋白。如果我们的干预措施能有效延缓自身免疫或最终延缓其进展为临床糖尿病，那么这项有史以来第一项 T1D 一级预防研究将对个人和全球社会产生深远的影响。