Trial to Reduce IDDM in the Genetically at Risk: A Nutritional primary prevention

减少遗传风险人群 IDDM 的试验：营养一级预防

基本信息

批准号：
8486292
负责人：
DOROTHY J BECKER
金额：
$ 168万
依托单位：
UNIVERSITY OF PITTSBURGH AT PITTSBURGH
依托单位国家：
美国
项目类别：
财政年份：
2001
资助国家：
美国
起止时间：
2001-09-27 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8486292
关键词：
10 year old 6 year old Address Affect Ancillary Study Autoantibodies Autoimmunity Breast Feeding Caseins Cattle Child Clinical Control Groups Country DNA Data Development Diabetes Mellitus Diabetes prevention Dietary Proteins Double-Blind Method Drops Early Diagnosis Enrollment European Exposure to Extravasation Family First Degree Relative Frequencies Funding Genotype Human Human Milk Immunity Incidence Individual Infant Infant formula Infection Insulin-Dependent Diabetes Mellitus International Intervention Intestines Life Measurement Measures Metabolic Milk Milk Proteins Mothers Natural History Nutrient Nutritional Patient Care Peripheral Blood Mononuclear Cell Pilot Projects Population Prediabetes syndrome Primary Prevention Proteins Randomized Controlled Trials Relative Risks Research Design Risk Risk Factors Rodent Rodent Model Role Self Tolerance Serum Societies T-Lymphocyte Testing Weaning abstracting base casein hydrolysate cost crosslink data management diabetes risk disorder risk feeding indexing infancy islet meetings prevent protein complex repository serological marker therapy design

项目摘要

DESCRIPTION (provided by applicant): Abstract: 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 allow 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 US coordinating and clinical centers for this 17 year study which is submitted in tandem with those of the European coordinating center and clinical centers and that of the Data Management Unit.

描述（由申请人提供）：摘要：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 1 型疾病风险遗传易感儿童的糖尿病 (T1D) 与啮齿动物模型中的情况一样。具体目标是： I-a：确定断奶后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：确定断奶后使用酪蛋白水解物是否会降低临床糖尿病的发生率。针对具有受影响的一级亲属和风险相关 HLA 基因型的受试者的随机对照试验目前已进入第 9 个年头。由 15 个国家的 77 个中心组成，已成功完成 2160 名符合条件的婴儿的登记，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的效果的 6-8 个月干预已于2007 年。由母亲自行决定的母乳喂养持续时间与背景人群相似或高于背景人群。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（6 岁时的终点）以及糖尿病的临床和/或代谢指数（10 岁时的终点）。目前，所有计划参数均已满足，退出率 < 2%，符合预期水平。存储血清、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。该申请涵盖了美国协调和临床中心这项为期 17 年的研究的 11-15 年，该申请与欧洲协调中心和临床中心以及数据管理部门的申请同时提交。