DIABETES PREVENTION TRIAL-IDDM (DPT-1)

糖尿病预防试验-IDDM (DPT-1)

• 批准号: 2016674
• 负责人: JAY S SKYLER
• 金额: $ 208.16万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1999-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2016674
• 关键词: autoantibody; clinical trials; cooperative study; data collection; diabetes mellitus genetics; disease /disorder prevention /control; genetic markers; human subject; insulin dependent diabetes mellitus; oral tolerance; pancreatic islet function; prediabetic state

Type I or insulin-Dependent Diabetes Mellitus (IDDM) arises in genetically predisposed individuals as consequence of immune mediated destruction of the pancreatic islet insulin secreting beta-cells. The onset of clinical symptoms of diabetes represents the end point of a chronic progressive decline in beta-cell function, and occurs when the majority of beta-cells have been lost. Since type 1 diabetes develops insidiously from an ongoing, immune-mediated destructive process, and it can be predicted with some degree of accuracy, then it is possible that intervention at a point in this long prodromal period would prevent the initiation or perpetuation of beta-cell destruction. A number of potential intervention strategies exist that may slow the course or prevent the development of type I diabetes, and/or preserve beta-cell function and thus stabilize individuals with new onset type 1 diabetes. The Prevent Diabetes Group (PDG) has been organized on the premise that significant advances can be made by a cooperative approach to the design and conduct of human clinical intervention trials both to prevent development of type I diabetes mellitus and to preserve beta-cell function in recent onset type I diabetes mellitus. The goal is to create a dynamic and flexible environment where investigators can work together to develop and implement research protocols. Each member of the group supports the concept of inter-institutional studies by pooling clinical case material and laboratory resources with other collaborating members, and of participating in study committees for the purpose of developing new ideas and analyzing or evaluating the results of studies related to the prevention and/or stabilization of human type I diabetes mellitus. For the purposes of these studies, the disease is divided into several stages of development (early, advanced, and late prediabetes; new onset diabetes; etc.). The purpose of dividing subjects into these disease stages is that different intervention strategies might be tested in different groups. For example, one might be willing to accept a greater risk of side effects in late disease, e.g. new onset type I diabetes, than in any of the stages of prediabetes. Likewise, one might accept greater risk in late prediabetes than in early or advanced prediabetes. Moreover, different strategies may seem more applicable in one category than another. The PDG is made up of member institutions (clinical centers) and investigators organized into Committees, and facilitated by an Operations Office, a Statistical Office, and several Reference Laboratories. This provides the basic stricture for an ongoing series of trials. The Reference laboratories will assure standardized, reliable methods are used. Predictive models will be compared. In addition, we propose to conduct and monitor two pilot and feasibility studies to test the potential of intervention with [1] periodic courses of intravenous insulin, with or without accompanying chronic subcutaneous insulin, and [2] gut antigen presentation by oral administration of potential autoantigens to induce immunological tolerance.

I型或胰岛素依赖型糖尿病(IDDM)发生在基因上 易感个体作为免疫介导性破坏的结果 胰岛分泌胰岛素的β细胞。临床的开始 糖尿病的症状代表着慢性进行性疾病的终点 贝塔细胞功能下降，当大多数贝塔细胞 已经迷失了。由于1型糖尿病是由一种 正在进行的，免疫介导的破坏性过程，可以用 一定程度的精确度，那么有可能在某一点上进行干预 在这漫长的前驱期内，将会阻止 对β细胞的破坏。一些潜在的干预策略 存在可能减缓进程或阻止I型糖尿病发展的 糖尿病，和/或保留β细胞功能，从而稳定下来 新发的1型糖尿病患者。预防糖尿病小组 (PDG)的组织前提是可以取得重大进展 由人类临床设计和实施的合作方法提出 既可预防I型糖尿病发展的干预试验 新近发病的I型糖尿病患者的胰岛β细胞功能 糖尿病。我们的目标是创造一个动态和灵活的 调查人员可以共同努力开发和实施的环境 研究方案。该小组的每个成员都支持 跨机构研究通过汇集临床病例材料和 与其他合作成员的实验室资源，以及 参加学习委员会，以开发新想法为目的 以及分析或评估与以下方面相关的研究结果 预防和/或稳定人类I型糖尿病。对于 这些研究的目的是将疾病分为几个阶段 发展(早期、晚期和晚期前驱糖尿病；新发糖尿病； 等)。将受试者划分为这些疾病阶段的目的是 在不同的人群中可以测试不同的干预策略。为 例如，一个人可能愿意接受更大的副作用风险 迟发性疾病，例如新发的I型糖尿病，比 糖尿病前期。同样，一个人可能会接受晚期糖尿病前期更大的风险。 而不是早期或晚期的糖尿病前期患者。此外，不同的策略可能 似乎更适用于一个类别而不是另一个类别。PDG由以下部分组成 成员机构(临床中心)和调查人员组织成 各委员会，并由业务处、统计处、 和几个参考实验室。这提供了基本的限制 正在进行的一系列试验。参考实验室将确保 使用了标准化、可靠的方法。预测模型将是 比较一下。此外，我们建议进行和监督两个试点项目和 用于测试干预潜力的可行性研究[1] 定期静脉注射胰岛素，伴或不伴 慢性皮下胰岛素和[2]口服肠道抗原递呈 注射潜在自身抗原以诱导免疫性 宽容。