IMMUNOTHERAPY TRIAL IN NEW ONSET TYPE 1 DIABETES

描述（改编自应用程序） 我们提出了一个两组随机，部分盲，安慰剂对照的临床研究。 一项检验霉酚酸酯（MMF）单独或与 达克利珠单抗（DZB）将延长受试者的C肽产生期 新发I型糖尿病本研究的第二个目的是提供 用于验证胰岛免疫替代标志物的临床材料 贝塔细胞。这项研究将由芭芭拉戴维斯中心联合进行， 丹佛儿童糖尿病和西雅图弗吉尼亚梅森研究中心 并利用每年超过80例新发l型糖尿病的病例 在这些机构。本研究的代谢终点为空腹 以及刺激的C肽、血红蛋白Alc和总胰岛素剂量。水平 自身抗体和T细胞对胰岛自身抗原的反应性，两者都是 I型糖尿病特异性的替代免疫学参数， 跟踪了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。受试者编号允许80%的把握度 来检测5%水平上的显著差异。这项研究具有创新性 因为待测试的试剂先前未在I型中进行过评价， 糖尿病，但在自身免疫性疾病干预的合理选择。 建议的替代标记使用肽四聚体来识别和计数 抗原应答性T细胞。我们认为这项研究是及时的， 在10年的时间间隔内，已经开发了毒性免疫抑制剂， 由于发现环孢霉素在新发中保持C-肽产生 患者 我们的力量预测是基于我们以前广泛的干预研究 并且待测试的试剂的选择得到动物研究的支持。MMF是一种 心、肾、肝抗排斥治疗有效成分 受惠人士它对治疗牛皮癣有效。DZB anti-IL 2 选择用于与MMF一起使用的受体抗体在治疗 急性肾排斥反应发作。这些药物在临床使用中的安全性 证明了一项I型糖尿病试验的合理性，30%的新发受试者 在20分钟内检测HbAlc水平， 年

DESCRIPTION (adapted from the application) We propose a two arm randomized, partially blinded, placebo-controlled clinical trial to test the hypothesis that mycophenolate mofetil (MMF) alone or with daclizurnab (DZB) will prolong the period of C-peptide production in subjects with new onset type I diabetes. A second aim of this study will provide the clinical material for the validation of surrogate markers for immunity to islet Beta cells. The study will be conducted jointly by the Barbara Davis Center for Childhood Diabetes in Denver and the Virginia Mason Research Center in Seattle and takes advantage of the annual accrual of over 80 new onset type-l diabetes at these institutions. The metabolic end-points of this study will be fasting and stimulated C-peptide, hemoglobin Alc, and total insulin dose. Levels of autoantibodies and T cell reactivity to islet autoantigens, both of which are surrogate immunological parameters specific for type I diabetes, will be followed. Measures of immune modulation will include serologic and T cell reactivity to recall antigens. The subject number allows for 80 percent power to detect differences significant at a 5 percent level. The study is innovative in that the agents to be tested have not previously been evaluated in type I diabetes, but are rational choices for interventions in an autoimmune disorder. The proposed surrogate markers use peptide tetramers to identify and enumerate antigen-responsive T cells. We believe the study is timely in that far less toxic immunosuppressive agents have been developed in the 10 year interval since Cyclosporine was found to preserve C-peptide production in new-onset patients. Our power projections are based on our extensive previous intervention studies and the choice of agents to be tested is supported by animal studies. MMF is an effective component of anti-rejection treatment of heart, kidney and liver recipients. It is effective for the treatment of psoriasis. The DZB anti-IL2 receptor antibody selected for use with MMF is effective in the treatment of acute renal rejection episodes. The safety of these agents in clinical use justifies a trial in type I diabetes, where 30 percent of new onset subjects run HbAlc levels that put them at high risk for vascular disease within 20 years.