IMMUNOTHERAPY TRIAL FOR NEW ONSET TYPE 1 DIABETES

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 我们提出了一项多中心、3组、随机、盲法、安慰剂对照的前瞻性研究，以检验以下假设：霉酚酸酯（MMF）单药或霉酚酸酯与达克珠单抗（DZB）联合治疗将延长新发1型糖尿病受试者的C肽产生期。 代谢终点还将包括血红蛋白A1 c和总胰岛素剂量。 本研究的第二个目的是检查拟定治疗对免疫学效应替代标志物的影响，即疾病特异性终点（自身抗体决定簇、同种抗体的产生以及T细胞反应性和频率）和免疫学终点。 这项研究将由芭芭拉戴维斯儿童糖尿病中心和其他参与试验网网站，包括弗吉尼亚梅森研究中心在西雅图联合进行。 这项研究是创新的，因为要测试的药物以前没有在1型糖尿病中进行过评估，但它们是干预自身免疫性疾病的合理选择。 我们认为这项研究是及时的，因为自从发现环孢霉素可以保护新发患者的C肽产生以来，在10年的时间间隔内已经开发出毒性小得多的免疫抑制剂。 我们的功率预测是基于广泛的先前的干预研究和选择的代理人进行测试是由动物研究的支持。 霉酚酸酯是心、肾、肝移植受者抗排斥治疗的有效成分。 它对治疗牛皮癣有效。 选择与MMF联合使用的DZB抗IL 2受体抗体可有效治疗急性肾排斥反应。 这些药物在临床使用中的安全性证明了在1型糖尿病中进行试验的合理性，其中30%的新发受试者的HbA 1c水平使他们在20年内处于血管疾病的高风险。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We propose a multicenter, 3-arm randomized, blinded, placebo-controlled prospective study to test the hypothesis that mycophenolate (MMF) alone or MMF with daclizumab (DZB) will prolong the period of c-peptide production in subjects with new onset type 1 diabetes. Metabolic end-points will also include hemoglobin A1c and total insulin dose. A second aim of the study will examine the effect of the proposed treatment on surrogate markers for immunologic effects, namely disease-specific endpoints (autoantibody determinants, generation of alloantibodies, and T cell reactivity and frequency) and immunological endpoints. The study will be conducted jointly by the Barbara Davis Center for Childhood Diabetes and other participating TrialNet sites including the Virginia Mason Research Center in Seattle. The study is innovative in that the agents to be tested have not previously been evaluated in type 1 diabetes, but are rational choices for interventions in an autoimmune disorder. 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 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 treatment of acute renal rejection episodes. The safety of these agents in clinical use justifies a trial in type 1 diabetes, where 30% of new onset subjects run HbA1c levels that put them at high risk for vascular disease within 20 years.