Type 1 Diabetes TrialNet at Indiana University Clinical Center

描述（由申请人提供）：1型糖尿病发生于遗传易感个体，是胰岛分泌胰岛素的β细胞免疫介导破坏的结果。糖尿病临床症状的出现代表了β细胞功能慢性进行性衰退的一个相对终点，并且发生在β细胞质量优势丧失的时候。糖尿病预防1型试验（DPT-1）和1型糖尿病试验网（Type 1 Diabetes TrialNet）表明：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)1型糖尿病患者亲属中存在自身抗体和胰腺β细胞功能障碍的证据可以高度准确地预测1型糖尿病。这些研究使大量患者在高血糖发作前的疾病早期阶段得以识别。

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.