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: 9307898
• 负责人: JEFFREY P KRISCHER
• 金额: $ 77.32万
• 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 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307898
• 关键词: 14 year old; Address; Affect; Age; Ancillary Study; Antibodies; Antigens; Appearance; Australia; Autoantibodies; Autoimmunity; Biological; Birth; Breast Feeding; Caseins; Cattle; Child; Clinical; Country; DNA; Data; Data Analyses; Data Set; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diet; Dietary Proteins; Disease; Disease Progression; Double-Blind Method; Dropout; Eligibility Determination; Enrollment; Ensure; Europe; Exposure to; Extravasation; First Degree Relative; Frequencies; Funding; Genotype; Human; Human Milk; Immunity; Immunologic Markers; Incidence; Infant; Infant formula; Infection; Insulin-Dependent Diabetes Mellitus; International; Intervention; Intestines; Laboratories; Manuscripts; Measurement; Measures; Metabolic; Milk; Milk Proteins; Mothers; Natural History; Nutrient; Outcome; Peripheral Blood Mononuclear Cell; Population; Prediabetes syndrome; Preparation; Prevention trial; Primary Prevention; Proteins; Protocols documentation; Puberty; Publishing; Randomized Controlled Trials; Relative Risks; Reporting; Risk; Rodent; Rodent Model; Role; Sampling; Self Tolerance; Study Subject; T-Lymphocyte; Testing; Time; Universities; Weaning; arm; base; casein hydrolysate; crosslink; data management; design; diabetes risk; disorder risk; feeding; follow-up; gut microbiome; indexing; islet; prevent; public health relevance; repository; therapy design

 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.

 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’)的完成将决定断奶是否像在啮齿动物模型中那样，断奶使用一种(外来)蛋白质已被广泛水解的配方，从而降低遗传易感儿童的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是否可以降低临床糖尿病的发生率；i-b：评估在使用水解研究公式治疗的组中，自身抗体和T1D的年龄调整后发病率(而不是累积发病率)是否发生了潜在的变化。这项历时最长、规模最大的双盲随机对照试验目前已进入第14个年头，受试者中有受影响的一级亲属和风险相关的人类白细胞抗原基因。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。2159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和标准牛奶断奶配方的效果。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。所有受试者在干预期内和干预后至少10年内被跟踪，测量完整牛奶暴露的免疫标记物、糖尿病预测自身抗体和糖尿病的临床和/或代谢指标(终点为10-14岁)。目前已达到所有规划指标，辍学率为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、交叉链接的储存库允许独立资助与糖尿病前期的自然病史和假说相关的辅助和机制研究。本申请涵盖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的研究中心的16-18年，该申请是与美国协调中心和临床中心的研究中心和数据管理单位的研究中心一起提交的。要求提供资金以完成试验并报告结果。