Trial to Reduce IDDM in the Genetically at Risk Study

遗传风险研究中减少 IDDM 的试验

• 批准号: 6319660
• 负责人: HANS K AKERBLOM
• 金额: $ 143.01万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6319660
• 关键词: Scandinavian country; autoantibody; baby food; breast feeding; caseins; diabetes mellitus genetics; diet therapy; dietary supplements; disease /disorder prevention /control; genetic screening; genetic susceptibility; human subject; human therapy evaluation; hydrolysis; infant human (0-1 year); insulin dependent diabetes mellitus; milk; mother /embryo /fetus nutrition; nutrition related tag; pathogenic diet; patient oriented research; proteolysis; weaning

The overall objective of the project is to determine whether weaning to a casein hydrolysate (Nutramigen/Tm) during at least the first 6 months of life reduces the incidence of Type 1 diabetes in genetically susceptible children. Specific Aims: I-a:To determine, if weaning to casein hydrolysate reduces the frequency of diabetes-predictive autoantibodies in subjects with risk-associated HLA genotype and a first degree relative with type 1 diabetes: I-b: To determine, if weaning to casein hydrolysate reduces the frequency of clinical diabetes in subjects with risk-associated HLA genotype and an affected first degree relative. Newborn infants, who have an increased genetic risk and first degree relatives with type 1 diabetes (mother, father or sibling has the disease, and HLA genotyping shows the subject to belong to the increased risk group) will be invited for the study. An international, multicentre, double blink, randomized, controlled trial of two different nutritional supplements will be performed. The newborn infants will be randomly allocated to receive after breast feeding one of two formulas during at least the first 6 months of life (the intervention period). The test formula will be a casein hydrolysate, free of intact cow's milk proteins. The casein hydrolysate is not diabetogenic in the NOD mouse. The control formula will be similar to a commonly used cow milk-based instant formula. Subjects will be followed during and after the intervention period for 6 and 10 years time during which serological markers are measured and the development of diabetes will be recorded. Such a clinical trial is necessary to get a definite answer to the hypothesis. Recruitment is carried out during a 2-year period in the U.S., Canada and 15 other countries. The estimated number of subjects participating in the randomized nutritional prevention study is approximately 2,800. This requires that genetic screening would be performed in approximately 6,200 newborn infants. The study question has important public health implications.

该项目的总体目标是确定至少在生命的前 6 个月内断奶使用酪蛋白水解物 (Nutramigen/Tm) 是否可以降低遗传易感儿童的 1 型糖尿病发病率。具体目标： I-a：确定断奶使用酪蛋白水解物是否会降低具有风险相关 HLA 基因型和 1 型糖尿病一级亲属的受试者中糖尿病预测自身抗体的频率： I-b：确定断奶使用酪蛋白水解物是否会降低具有风险相关 HLA 基因型和受影响的一级亲属的受试者中临床糖尿病的频率。遗传风险增加的新生儿和患有 1 型糖尿病的一级亲属（母亲、父亲或兄弟姐妹患有该疾病，并且 HLA 基因分型显示受试者属于风险增加组）将被邀请参加研究。将对两种不同的营养补充剂进行国际、多中心、双眨眼、随机、对照试验。新生儿将被随机分配在至少出生后的前 6 个月（干预期）内接受两种配方奶粉中的一种母乳喂养。测试配方是酪蛋白水解物，不含完整的牛奶蛋白。酪蛋白水解物不会导致 NOD 小鼠患糖尿病。对照配方将类似于常用的基于牛奶的速溶配方。将在干预期间和之后对受试者进行为期 6 年和 10 年的跟踪，在此期间测量血清学标志物并记录糖尿病的发展情况。为了得到该假设的明确答案，这样的临床试验是必要的。招募为期两年，在美国、加拿大和其他 15 个国家/地区进行。参与随机营养预防研究的受试者人数估计约为 2,800 人。这需要对大约 6,200 名新生儿进行基因筛查。该研究问题具有重要的公共卫生意义。