ORAL INSULIN FOR PREVENTION OF DIABETES IN RELATIVES AT RISK FOR TYPE 1 DIABE

口服胰岛素可预防有 1 型糖尿病风险的亲属患糖尿病

• 批准号: 7950888
• 负责人: GARY Lee FRANCIS
• 金额: $ 0.19万
• 依托单位: VIRGINIA COMMONWEALTH UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950888
• 关键词: American; Animals; Antigens; Autoantibodies; Autoantigens; Autoimmunity; Beta Cell; Categories; Characteristics; Clinical; Clinical Research; Cohort Analysis; Computer Retrieval of Information on Scientific Projects Database; Development; Diabetes Mellitus; Diabetes prevention; Enrollment; Funding; Glucose; Goals; Grant; Human; Hyperglycemia; Immune; Immune Tolerance; Immunologics; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Metabolic; Metabolic Marker; Oral; Oral Administration; Phenotype; Placebos; Randomized; Recombinants; Recruitment Activity; Relative (related person); Research; Research Personnel; Resources; Risk; Risk Factors; Source; Symptoms; T-Lymphocyte; Testing; Time; United States National Institutes of Health; base; diabetes risk; immune function; prevent; primary outcome; response; treatment effect

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Hypothesis: The underlying hypothesis of this trial is the concept of induction of immunologic tolerance to the insulin secreting beta cell through the presentation of the autoantigen (insulin) orally. Animal studies have suggested that tolerance is accompanied by characteristic changes in immune phenotypes; however, whether these changes are associated with tolerance induction in humans is unknown. A goal of this study therefore, will be to study immune function through studies of B and T cell phenotype and function including antigen specific responses. Specific Aims: The primary outcome is the elapsed time from random treatment assignment to the development of diabetes among those enrolled in the primary analysis cohort consisting of subjects with insulin autoimmunity and absence of metabolic abnormalities. Criteria for diabetes onset are as defined by the American Diabetes Association (ADA) based on glucose testing, or the presence of symptoms and unequivocal hyperglycemia. The primary objective is to determine whether intervention with repeated oral administration of recombinant human insulin will prevent or delay the development of clinical Type 1 Diabetes Mellitus (T1DM) in subjects at risk for T1DM. Secondary objectives include the description of the effects of treatment with oral insulin versus placebo in other categories of subjects defined using different combinations of autoantibodies and metabolic status (the Secondary Analysis Strata) and an assessment of the consistency of treatment effect among strata. Secondary objectives also include the assessment of the effects of treatment on immunologic and metabolic markers, and the association of these markers with the risk of diabetes onset, among other possible risk factors. The operational objectives are to recruit, screen, randomize, and follow sufficient numbers of subjects to provide adequate statistical power to determine whether T1DM can be delayed through the administration of oral insulin.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 假设：该试验的基本假设是通过口服自身抗原（胰岛素）诱导胰岛素分泌β细胞的免疫耐受性的概念。动物研究表明，耐受性伴随着免疫表型的特征变化。但是，这些变化是否与人类的耐受性诱导有关。因此，这项研究的目的是通过研究B和T细胞表型和功能（包括抗原特定反应）来研究免疫功能。 具体目的：主要结果是从随机治疗分配到参与主要分析队列的患者的糖尿病的发展的时间是，由胰岛素自身免疫性和缺乏代谢异常组成的受试者组成。糖尿病发作的标准是根据葡萄糖测试或症状和明确的高血糖的存在的美国糖尿病协会（ADA）所定义的。主要目的是确定重组人胰岛素重复给药的干预是否会阻止或延迟在有T1DM风险的受试者中临床1型糖尿病（T1DM）的发展。次要目标包括用不同的自身抗体和代谢状态（二级分析阶层）定义的其他类别的受试者中口服胰岛素与安慰剂治疗的影响，以及对层之间治疗效应的一致性的评估。次要目标还包括评估治疗对免疫学和代谢标记的影响，以及这些标志物与糖尿病发作风险的关联以及其他可能的危险因素。操作目标是招募，筛选，随机化和遵循足够数量的受试者，以提供足够的统计能力，以确定是否可以通过口服胰岛素来延迟T1DM。