IMMUNOTHERAPY TRIAL IN NEW ONSET TYPE 1 DIABETES

新发 1 型糖尿病的免疫治疗试验

• 批准号: 6460198
• 负责人: PETER A GOTTLIEB
• 金额: $ 2.5万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2003-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6460198
• 关键词: T lymphocyte; antigen antibody reaction; autoantibody; autoantigens; clinical research; clinical trials; combination therapy; cooperative study; disease /disorder onset; enzyme linked immunosorbent assay; human subject; human therapy evaluation; immunosuppressive; immunotherapy; insulin dependent diabetes mellitus; interleukin 2; monoclonal antibody; mycophenolate mofetil; outcomes research; polymerase chain reaction; prediabetic state; serology /serodiagnosis; statistics /biometry

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.

描述（根据应用程序改编） 我们提出了一个两臂随机，部分盲目的安慰剂控制的临床 试验以检验单独或与霉酚酸酯（MMF）或与之相关的假设 Daclizurnab（DZB）将延长受试者中C肽的产生周期 带有新的I型糖尿病。这项研究的第二个目标将为 验证替代标志物以免疫胰岛的临床材料 β细胞。该研究将由芭芭拉·戴维斯中心共同进行 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多种新发作型L糖尿病的年度计费 在这些机构。这项研究的代谢终点将是禁食 并刺激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，这两个都是 特定于I型糖尿病的替代免疫学参数将是 紧随其后。免疫调节的度量将包括血清学和T细胞 回忆抗原的反应性。该主题允许80％的功率 检测5％的差异。这项研究是创新的 因为要测试的代理以前尚未在I型中进行评估 糖尿病是自身免疫性疾病干预措施的合理选择。 提出的替代标记使用肽四聚体来识别和枚举 抗原反应性T细胞。我们认为这项研究及时少得多 有毒免疫抑制剂已在10年间隔开发 由于发现环孢素可以保留新的C肽的产生 患者。 我们的权力预测基于我们以前的大量干预研究 动物研究支持要测试的药物的选择。 MMF是一个 心脏，肾脏和肝脏抗反应治疗的有效组成部分 收件人。这对于牛皮癣治疗有效。 DZB抗IL2 与MMF一起选择的受体抗体可有效治疗 急性肾排斥发作。这些药物在临床用途中的安全性 证明I型糖尿病的试验是合理的，其中有30％的新发作受试者 运行HBALC水平，使它们在20之内患血管疾病的高风险 年。