Northwest Clinical Center for Type 1 Diabetes - TrialNet

描述(由申请者提供)：本申请重新被选为糖尿病试验网临床中心包括(1)一项拟议的临床试验(2)描述我们在进行1型糖尿病临床研究方面的活动(3)描述我们的招募工作，以及(4)描述可用于进行试验网方案的临床设施。 先前的研究表明，短期应用抗T细胞、抗B细胞和基于抗原的治疗至少可以暂时改变β细胞的破坏过程。要扩大治疗效果，可能需要联合治疗，如消除T效应器反应、保护β细胞、激活T调节细胞和增强胰岛素作用。TrialNet和其他团队已经成功开发了一个平台，可以快速测试新诊断对象的治疗方法。我们认为，对各种药物进行系统测试，并仔细使用临床样本进行探索性数据分析，是唯一的前进道路。 为此，我们建议测试Tocilizumab(抗IL6Rab)在最近诊断为1型糖尿病的受试者中的效果，以确定它是否可以保护β细胞功能。我们选择抗IL6Rab是基于以下观察结果：(1)从机制上讲，抗IL6Rab可能具有几个重要的效果：(1)从机制上讲，抗IL6Rab既是一种促进T调节细胞活性的疗法，可以延长疾病的缓解时间，也可以作为一种抗炎药物，改变局部胰腺炎症浸润，允许增强β细胞功能和/或增强胰岛素作用；(2)有关于使用抗IL6Rab的临床安全性数据，包括儿童数据；(3)抗IL6Rab在治疗其他自身免疫性疾病方面临床上是有效的。 这项试验的具体目的是： (在新诊断的患者中证明抗IL6Rab的短期安全性， (证明在新诊断的患者中，抗IL6Rab在保存 β细胞功能 (测试抗IL6Rab治疗和治疗反应对与我们主要假设的作用机制相关的措施的影响-促进T调节细胞的活动。 公共卫生相关性：1型糖尿病涉及免疫介导的胰岛素产生β细胞的破坏，导致终生依赖外源性胰岛素。1型糖尿病是儿童及其家庭的一种特殊负担，是最常见的儿童慢性疾病之一。一种可以延缓或阻止β细胞破坏的疗法将显著改善糖尿病患者的日常管理，并减少长期并发症，从而对T1 DM患者产生重大临床影响。

DESCRIPTION (provided by applicant): This application for re-selection as a Diabetes TrialNet Clinical Center consist of (1) a proposed clinical trial (2) a description of our activities in the conduct of Type 1 diabetes clinical research (3) a description of our recruitment efforts, and (4) a description of the clinical facilities available for the conduct of TrialNet protocols. Previous studies have demonstrated that short term administration of anti-T cell, anti-B cell, and antigen-based therapy at least temporarily alters the course of beta cell destruction. Extending therapeutic benefits will likely require combination therapy such as elimination of the T effector response, protection of beta cells, activation of T regulatory cells, and enhancement of insulin action. TrialNet and other groups have successfully developed a platform to rapidly test therapies in newly diagnosed subjects. We believe that systematic testing of a wide variety of agents and careful use of clinical samples for exploratory analysis of data is the only way forward. To that end, we propose to test the effect of Tocilizumab (Anti-IL6Rab) on recently diagnosed subjects with Type 1 diabetes to determine whether it will preserve beta cell function. Our selection of Anti- IL6Rab is based on the following observations: (1) mechanistically, Anti-IL6Rab may have several important effects both as a therapy promoting the activity of T-regulatory cells allowing prolonged remission of disease, and as an anti-inflammatory altering the local pancreatic inflammatory infiltrate allowing enhanced beta cell function and/or allowing enhanced insulin action, (2) there is clinical safety data on the use of Anti-IL6Rab including data in children, (3) Anti-IL6Rab is clinically efficacious in treatment of other autoimmune diseases. The specific aims of this trial are to: ( Demonstrate the short term safety of Anti-IL6Rab in newly diagnosed patients, ( Demonstrate the efficacy of Anti-IL6Rab in newly diagnosed patients with respect to preservation of beta cell function ( Test the impact of Anti-IL6Rab therapy and response to therapy on measures associated with our primary hypothesized mechanism of action - promoting the activity of T regulatory cells. PUBLIC HEALTH RELEVANCE: Type 1 diabetes involves immune mediated destruction of insulin producing beta cells leading to lifelong dependence upon exogenous insulin. T1DM is a particular burden to children and their families, representing one of the most common chronic childhood diseases. A therapy that could delay or halt beta cell destruction would significantly improve the day-to-day management for subjects with diabetes and reduce long-term complications, thereby having significant clinical impact on patients with T1DM.