Type 1 Diabetes TrialNet at Indiana University Clinical Center

描述（由申请人提供）：1型糖尿病发生在遗传易感个体中，是免疫介导的胰岛胰岛素分泌β细胞破坏的结果。糖尿病的临床症状的发作代表β细胞功能的慢性进行性下降中的相对终点，并且当β细胞质量的优势丧失时发生。糖尿病预防试验-1型（DPT-1）和1型糖尿病TrialNet显示：1）1型糖尿病的多中心合作研究可以在国家和国际层面上有效协调，2）通过自身抗体的存在和胰腺β-淀粉样蛋白的证据，可以在1型糖尿病患者亲属中高度准确地预测1型糖尿病。细胞功能障碍这些研究使得能够在高血糖症发作之前的疾病的非常早期阶段识别大量患者。 在1型糖尿病动物模型和人体试验中的证据表明，可以利用多种干预措施改变β细胞破坏的过程。越来越多地，在其他自身免疫性疾病的研究和器官移植领域的新的免疫剂的特点，已被提出用于治疗自身免疫性糖尿病。一种这样的药剂，抗CD 20药物利妥昔单抗（RituxanR，Genentech，South San弗朗西斯科和Biogen），最初开发用于治疗B细胞淋巴瘤，现在被批准用于治疗类风湿性关节炎，另一种典型的T细胞介导的疾病。TrialNet利妥昔单抗新发干预研究的结果，由共同PI为这项研究提案设计的Mark Pescovitz博士，现在已经为这种治疗方式在1型糖尿病中的安全性和有效性提供了证据。 我们建议延长和扩大我们作为临床中心参与1型糖尿病试验网。作为建议在新发干预试验中使用利妥昔单抗的临床中心和该研究受试者招募的领导者，IU唯一有资格使用该药物进行预防研究。 公共卫生相关性：本申请是根据RFA-DK-08-011征求邀请临床试验机构申请成为TrialNet临床中心。各中心将开展TrialNet自然史研究以及预防和新发干预研究，同时监督附属中心和其他临床研究中心的网络，这些中心将招募和随访T1 D患者和有疾病发展风险的患者。

DESCRIPTION (provided by applicant): Type 1 diabetes arises in genetically predisposed individuals as a consequence of the immune-mediated destruction of the pancreatic islet insulin secreting beta cells. The onset of clinical symptoms of diabetes represents a relative endpoint in the chronic progressive decline of beta cell function, and occurs when a preponderance of beta cell mass is lost. The Diabetes Prevention Trial -Type 1 (DPT-1) and Type 1 Diabetes TrialNet have shown: 1) that multi-center cooperative research in type 1 diabetes can be efficiently coordinated on a national and international level and 2) that type 1 diabetes can be predicted with a high degree of accuracy in relatives of patients with type 1 diabetes by the presence of autoantibodies and evidence of pancreatic beta-cell dysfunction. These studies have enabled identification of a large number of patients at the very early stages of their disease prior to the onset of hyperglycemia. Evidence, both in animal models of type-1 diabetes and in human trials, has shown that it is possible to alter the course of beta cell destruction utilizing numerous interventions. Increasingly, novel immunologic agents characterized in investigations of other autoimmune disorders and in the field of organ transplantation have been proposed for the treatment of autoimmune diabetes. One such agent, the anti-CD20 drug rituximab (RituxanR, Genentech, South San Francisco and Biogen) originally developed for treatment of B-cell lymphoma, is now approved for treatment of rheumatoid arthritis, another classically T-cell mediated disease. Results of the TrialNet Rituximab new-onset intervention study, designed by the Co-PI for this study proposal Dr. Mark Pescovitz, has now provided evidence for safety and efficacy of this treatment modality in type 1 diabetes. We propose to extend and expand our participation in Type 1 Diabetes TrialNet as a Clinical Center. As the Clinical Center that proposed the use of rituximab in a new-onset intervention trail and the leader in subject recruitment for that study, IU is uniquely qualified to conduct a prevention study utilizing this agent. PUBLIC HEALTH RELEVANCE: This application is in accordance with the RFA-DK-08-011 solicitation to invite sites to apply to become TrialNet Clinical Centers. Centers will carry out the TrialNet Natural History Study and prevention and new-onset intervention studies while overseeing a network of Affiliate Centers and additional clinical sites that will recruit and follow individuals with T1D and those at risk for development of the disease.