Type 1 Diabetes TrialNet at Indiana University Clinical Center

 描述(由申请人提供)：1型糖尿病(T1D)出现在遗传易感的个体中，是免疫介导的胰岛分泌胰岛素的β细胞破坏的结果。糖尿病临床症状的出现代表了胰岛β细胞功能慢性进行性下降的相对终点，当大部分胰岛细胞团块丧失时就会发生。1型糖尿病预防试验(DPT-1)和1型糖尿病试验网络已经证明：1)国内和国际层面上可以有效地协调T1D的多中心合作研究，2)通过自身抗体和其他易感代谢和遗传因素的存在，可以在显著高血糖之前高度准确地预测T1D患者的亲属的T1D。这些研究使人们能够在疾病的早期阶段识别出大量的个体。TrialNet网络致力于进一步确定T1D发展的病理生理学，并对可能导致T1D预防和/或改善的介入剂进行临床试验。印第安纳大学(IU)自2003年成立以来一直是TrialNet联盟的重要成员，最初是作为DPT-1研究的美国地区招募中心，然后是TrialNet的关键临床中心，拥有广泛的附属网络，位于中西部和东部地区的十字路口。为了响应RFA DK-14-016，我们在TrialNet上概述了我们迄今取得的成就，重点是TrialNet试验和研究方面的领导力、我们对协作研究的支持、我们的招聘和拓展计划(包括使用印第安纳州、伊利诺伊州、密歇根州、肯塔基州和俄亥俄州的附属网站)、我们的后续和保留计划，以及提高网络成本效益的建议。我们展示了我们通过预防之路研究对T1D患者亲属进行筛查的出色比率；我们在监测、预防、新发和长期跟踪研究方面的坚实登记和出色保留率；以及我们通过9个地区站点扩展的附属网络。此外，我们还参与了一项用于预测和监测T1D进展的生物标记物发现计划，并正在使用印第安纳临床和翻译科学研究所的核心资源来识别新的患者群体，并探索参与开放研究方案的参与者的研究障碍。

 DESCRIPTION (provided by applicant): Type 1 diabetes (T1D) arises in genetically predisposed individuals as a consequence of the immune- mediated destruction of 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 Network have demonstrated that: 1) multi-center cooperative research in T1D can be efficiently coordinated on a national and international level and 2) T1D can be predicted with a high degree of accuracy in relatives of persons with T1D by the presence of autoantibodies and other predisposing metabolic and genetic factors prior to significant hyperglycemia. These studies have enabled identification of a large number of individuals at very early stages of disease. The TrialNet network is committed to further define the pathophysiology of the development of T1D and to conduct clinical trials of interventional agents that may lead to the prevention and/or amelioration of the disease. Indiana University (IU) has been a key member of the TrialNet consortium since its inception in 2003, first as an U.S. Regional Recruitment Center for the DPT-1 study and then as a critical Clinical Center for TrialNet with a wide affiliate network, centrally positioned at the crossroads of Midwestern and Eastern regions. In response to RFA DK-14-016 we outline our accomplishments to date in TrialNet, with a particular focus on leadership in TrialNet trials and studies, our support of collaborative research, our recruitment and outreach plans (including use of affiliate sites in Indiana, Illinois, Michigan, Kentucky, and Ohio), our follow-up and retention plans, and suggestions for increasing the network's cost efficiency. We demonstrate our excellent rates of screening of relatives of persons with T1D through the Pathway to Prevention Study; our solid enrollment and excellent retention for monitoring, prevention, new-onset, and long-term follow-up studies; and our affiliate network expansion by 9 regional sites. In addition, we are engaged in a program of biomarker discovery for prediction and monitoring of progression of T1D and are using the Indiana Clinical and Translational Sciences Institute core resources to identify new patient populations and to explore research barriers to participant participation in open study protocols.