TrialNet: DiabetesType 1 Prevention Trial

描述（由申请人提供） 长期目标：确定早期介入治疗是否可以 1型糖尿病的治疗方法有哪些？具体目标： 糖尿病前期和新发糖尿病受试者的干预试验 糖尿病预防试验-1型（DPT-1）：以确定是否早期 1型糖尿病患者非糖尿病亲属胰岛素干预应用 1型糖尿病可以延缓其作为临床疾病的发展。 胰岛素用于此目的，因为它是一种良好表征的抗原 是由β细胞产生的研究设计：肠外抗原 方案入组的受试者被发现处于高风险（大于50%） 在未来5年内患糖尿病的风险。受试者随机分配至 胰岛素治疗组每年静脉注射胰岛素4天， 每天两次注射超长效（早餐前和睡前）。 口服抗原方案招募发现处于中等风险的受试者 （25- 50%）在未来5年内发展为1型糖尿病。 这是一项双盲研究，所有受试者每天服用1粒胶囊， 接受抗原，其他人接受安慰剂。抗体水平， 随后是胰岛素、C肽、HbA 1C和葡萄糖。主要研究终点为 两个？有糖尿病吗口服葡萄糖耐量试验（OGTT）在不同的日子进行。 新发1型糖尿病的免疫治疗试验：检验以下假设： 霉酚酸酯（单用MMF或与达克珠单抗（DZB）合用）将延长 在新发1型糖尿病受试者中的C肽产生期。一 第二个目的是提供临床资料， 对胰岛β细胞免疫的替代标志物。本研究具有创新性， 这些代理人没有事先评估，但理性的选择， 用于干预自身免疫性疾病 研究设计：自身抗体水平和T细胞对胰岛的反应性 自身抗原，两者都是特异性的替代免疫学参数， 1型糖尿病将被随访。免疫调节的措施将包括 血清学和T细胞对回忆抗原的反应性。代谢终点 这项研究将空腹和刺激C肽，血红蛋白A1 C，和总 胰岛素剂量。如果这项研究有积极的结果，那么我们将提出一个 在1型糖尿病高危人群中进行了类似的研究。

DESCRIPTION (provided by applicant) Long Term Objective: to determine whether early interventional therapies can delay, prevent, or reverse the development of Type 1 diabetes. Specific Aims: intervention trials for subjects with pre-diabetes and new onset diabetes The Diabetes Prevention Trial - Type 1 (DPT-1): to determine whether the early intervention use of insulin in nondiabetic relatives of persons with Type 1 diabetes can delay their development of Type 1 diabetes as a clinical disease. Insulin is used for this purpose since it is a well characterized antigen specifically produced by beta cells. Research design: the parenteral antigen protocol enrolled subjects found to be at high risk (greater than 50 percent) for development of diabetes in the next 5 years. Subjects randomized to the insulin-treated group received insulin intravenously for 4 days each year and two injections of Ultralente each day (before breakfast and before bedtime). The oral antigen protocol enrolls subjects found to be at intermediate risk (25-50 percent) for the development of Type 1 diabetes in the next 5 years. This is a double-blind study and all subjects take 1 capsule daily, with half receiving the antigen and the others receiving a placebo. Levels of antibodies, insulin, C-peptide, HbA1C and glucose are followed. The main study endpoint is two ?diabetic? oral glucose tolerance tests (OGTT) performed on different days. Immunotherapy Trial in New Onset Type 1 Diabetes: to test the hypothesis that mycophenolate mofetil (MMF alone or with daclizumab (DZB) will prolong the period of C-peptide production in subjects with new onset Type 1 diabetes. A secondary aim is to provide the clinical material for the validation of surrogate markers for immunity to islet beta-cells. This study is innovative in that these agents have not been previously evaluated but are rational choices for intervention in an autoimmune disorder. Research design: Levels of autoantibodies and T cell reactivity to islet autoantigens, both of which are surrogate immunological parameters specific for Type 1 diabetes will be followed. Measures of immune modulation will include serologic and T cell reactivity to recall antigens. The metabolic end-points of this study will be fasting and stimulated C-peptide, hemoglobin A1C, and total insulin dose. If this study has a positive outcome, then we would propose a similar study in people at high risk for developing Type 1 diabetes.