DPT-1 / TrialNet

描述(由申请人提供) 长期目标：确定早期介入治疗是否可以 延缓、预防或逆转1型糖尿病的发展。具体目标： 糖尿病前期和新发糖尿病患者的干预试验 1型糖尿病预防试验(DPT-1)：确定早期 胰岛素在1型糖尿病患者非糖尿病亲属中的干预使用 糖尿病可以延缓1型糖尿病作为一种临床疾病的发展。 胰岛素被用于这一目的，因为它是一种特性良好的抗原。 特别是由β细胞产生的。研究设计：肠外抗原 方案登记的受试者被发现处于高危状态(大于50%) 在未来5年内发展为糖尿病。受试者被随机分配到 胰岛素治疗组每年静脉注射胰岛素4天， 每天两次注射Ultraalente(早餐前和睡前)。 口服抗原方案招募被发现处于中等风险的受试者 (25%-50%)用于在未来5年内发展成1型糖尿病。 这是一项双盲研究，所有受试者每天服用一粒胶囊，每次一半 接受抗原治疗，其他人接受安慰剂治疗。抗体水平， 其次是胰岛素、C-肽、糖化血红蛋白和葡萄糖。主要研究终点是 两个？糖尿病？不同时间进行口服葡萄糖耐量试验(OGTT)。 新发1型糖尿病的免疫治疗试验：验证以下假设 霉酚酸酯(MMF)单独或与Daclizumab(DZB)合用可延长 新发1型糖尿病患者的C-肽产生周期。一个 次要目的是为临床验证提供材料。 胰岛β细胞免疫的替代标记物。这项研究在以下方面具有创新性 这些药物以前没有经过评估，但都是理性的选择 对自身免疫性疾病的干预。 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 接下来将是1型糖尿病。免疫调节措施将包括 血清学和T细胞反应性以召回抗原。新陈代谢的终点 这项研究将禁食和刺激C-肽、血红蛋白A1C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 在患1型糖尿病的高危人群中进行类似的研究。

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.