Trial to Reduce IDDM in the Genetically at Risk- study

减少遗传风险研究中 IDDM 的试验

• 批准号: 7647429
• 负责人: Mikael Knip
• 金额: $ 243.88万
• 依托单位: UNIVERSITY OF HELSINKI
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-26 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7647429
• 关键词: 10 year old; 6 year old; Achievement; Address; Adverse event; Affect; Age; Aliquot; Alleles; American; Ancillary Study; Animals; Antibodies; Autoantibodies; Autoimmune Diabetes; Autoimmunity; Award; Beta Cell; Blood specimen; Breast Feeding; Caseins; Cataloging; Catalogs; Cattle; Cells; Child; Clinical; Clinical Trials Design; Clinical Trials Network; Complex; Consensus; Controlled Clinical Trials; Country; DNA; Data; Data Collection; Development; Diabetes Mellitus; Diabetes prevention; Diet; Dietary Intervention; Dietary Proteins; Double-Blind Method; Drops; Enrollment; Environment; European; Evolution; Exclusive Breastfeeding; Exposure to; Extravasation; Family; First Degree Relative; Follow-Up Studies; Food; Frequencies; Funding; Funding Agency; Future; Generations; Genetic; Genetic Polymorphism; Genotype; Goals; Grant; Health Insurance Portability and Accountability Act; Health Policy; Human; Human Milk; Hydrolysis; Immunity; Incidence; Individual; Infant; Infection; Institution; Insulin-Dependent Diabetes Mellitus; International; Intervention; Intervention Trial; Intestines; Language; Life; Link; Logistics; Lymphocyte; Manuals; Measurement; Measures; Metabolic; Metabolism; Milk; Milk Proteins; Modification; Monitor; Mothers; Multicenter Trials; Natural History; Neonatal Screening; Newborn Infant; Online Systems; Peer Review; Peripheral Blood Mononuclear Cell; Phase; Phase I Clinical Trials; Pilot Projects; Placebo Control; Prediabetes syndrome; Pregnancy; Preparation; Primary Prevention; Procedures; Progress Reports; Proteins; Protocol Compliance; Protocols documentation; Public Health; Quality Control; Questionnaires; Randomized; Randomized Controlled Trials; Recruitment Activity; Relative Risks; Research Design; Research Ethics Committees; Research Infrastructure; Research Personnel; Risk; Rodent; Rodent Model; Role; Sampling; Secure; Self Tolerance; Serum; Shipping; Ships; Societies; Staging; Statistical Data Interpretation; System; T-Lymphocyte; Testing; Time; Training; Translating; Treatment Efficacy; United States National Institutes of Health; Visit; Vitamin D; Weaning; Work; base; casein hydrolysate; cohort; crosslink; data management; design; diabetes risk; disorder risk; follow-up; indexing; islet; meetings; prevent; prospective; receptor; repository; response; serological marker; web site

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.

描述（由申请人提供）： 降低遗传风险儿童胰岛素依赖型糖尿病的试验（TRIGR）将确定断奶至（外源）蛋白质已被广泛水解的配方食品是否会降低遗传易感儿童1型糖尿病（T1 D）的疾病风险，就像在啮齿动物模型中一样。具体目标是：I-a：确定断奶至水解酪蛋白配方（Nutramigen（tm））是否降低糖尿病预测性自身抗体的频率，和I-b：确定断奶至水解酪蛋白是否降低临床糖尿病的频率。这项双盲、随机对照试验在具有受影响的一级亲属和风险相关HLA基因型的受试者中进行，需要2032名合格婴儿：需要招募4516名新生儿，其中45%具有合格的HLA基因型（迄今为止为45.2%）。已经建立了一个国际多中心联盟，由15个国家的73个中心组成。到2005年1月底，我们完成了招募目标的65%，登记了3187名婴儿，2775名随机婴儿和1186名合格婴儿进入干预。6-8个月的干预旨在比较水解酪蛋白或基于标准牛奶的断奶配方的效果。母乳喂养的时间长短由母亲自行决定。招募和干预工作将在本试验继续实施提案的第二年完成。所有受试者在干预期间和之后随访10年，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）和糖尿病的临床和/或代谢指数（终点为10岁）。储存的血清、DNA和冷冻保存的外周血单核细胞的大型交联储存库允许独立资助的与前驱糖尿病的自然史和待检验的假设相关的辅助和机制研究。牛奶蛋白是人类最常见的完整的外来断奶蛋白。如果我们的干预措施能有效延缓自身免疫或其进展为糖尿病，那么这项首次T1 D一级预防研究将对个人和全球社会产生深远的影响。