IMMUNOTHERAPY TRIAL IN NEW ONSET TYPE 1 DIABETES

说明(改编自应用程序) 我们提出了一项双臂随机、部分盲、安慰剂对照的临床试验。 试验检验霉酚酸酯(MMF)单独或联合应用的假说 Daclizurnab(DZB)可延长受试者C肽的产生期 新发的I型糖尿病。这项研究的第二个目标将提供 胰岛免疫替代标志物验证的临床资料 β细胞。这项研究将由芭芭拉·戴维斯中心联合进行 丹佛的儿童糖尿病和西雅图的弗吉尼亚·梅森研究中心 并利用80多名新发病类型-L糖尿病的年累计额 在这些机构。这项研究的新陈代谢终点是禁食 并刺激C肽、糖化血红蛋白和总胰岛素用量。级别 自身抗体和T细胞对胰岛自身抗原的反应性，这两者都是 针对I型糖尿病的替代免疫学参数将是 紧随其后。免疫调节的措施将包括血清学和T细胞 召回抗原的反应性。受试者数量允许80%的能量 以检测5%水平上的显著差异。本研究具有创新性。 因为要测试的试剂以前没有在类型I中进行过评估 糖尿病，但对于自身免疫性疾病的干预是理性的选择。 建议的替代标记使用多肽四聚体来识别和计数 抗原反应性T细胞。我们认为这项研究是及时的，因为 有毒的免疫抑制剂在10年的时间间隔中被开发出来 自从环孢素被发现在新发病例中保存C-肽的产生 病人。 我们的力量预测是基于我们之前广泛的干预研究 而被测试试剂的选择也得到了动物研究的支持。MMF是一种 心、肾、肝抗排斥治疗有效成分 收件人。它对治疗牛皮癣很有效。DZB抗白介素2 选择与MMF联合使用的受体抗体对治疗慢性粒细胞白血病有效 急性肾排斥发作。这些药物临床使用的安全性 有理由进行I型糖尿病试验，30%的新发病受试者 运行HbAlc水平，使他们在20分钟内处于血管疾病的高危状态 好几年了。

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.