"Advancing Islet Transplant for Type 1 Diabetes Care"

描述（由申请人提供）： 胰岛移植提供了一种有前途的微创方法，以恢复正常血糖和胰岛素依赖性的1型糖尿病患者与低血糖意识。然而，它的临床适用性受到以下因素的影响：需要毒性免疫抑制药物，需要来自多个胰腺供体的胰岛以实现胰岛素非依赖性，以及移植后胰岛功能的长期下降。本申请中概述的方案是多中心、前瞻性、开放标签试验，通过评估3组1型糖尿病患者的胰岛功能和生存率来解决这些问题：1）接受标准化无类固醇、钙调磷酸酶抑制剂保留方案治疗的患者（临床胰岛移植（CIT）方案07）; 2）接受标准化免疫抑制方案以及免疫抑制药物脱氧精胍菌素治疗的患者（CIT方案03）;和3）具有功能性肾同种异体移植物的患者（CIT方案06）。这些协议最初由明尼苏达大学、西北大学和加州大学弗朗西斯科分校发起，作为CIT联盟的一部分。展望未来，根据NIH指令和RFA-DK-09-501，出于后勤原因，这三个中心的管理将分开，但研究中心将继续共享CIT前五年期间启动的知识、专业知识和方案。 相关性（由申请人提供）：本申请中概述的拟定临床方案旨在：1）检查在1型糖尿病受者的胰岛移植中，在标准化免疫抑制方案中移植围术期添加免疫抑制剂脱氧精胍菌素的影响; 2）检查1型糖尿病受者的胰岛移植结局和肾同种异体移植。我们相信，这些研究结果将提高胰岛移植的疗效，并有助于临床胰岛移植从临床研究过渡到临床护理。

DESCRIPTION (provided by applicant): Pancreatic islet transplantation offers a promising, minimally-invasive approach to restore normoglycemia and insulin independence in type 1 diabetics with hypoglycemic unawareness. However, its clinical applicability is compromised by the need for toxic immunosuppressive drugs, the need for islets from several pancreas donors to achieve insulin independence, and the long-term decline in islet function after transplantation. The protocols outlined in this application are multi-center, prospective, open-label trials that address these issues by assessing islet function and survival in 3 groups of patients with type 1 diabetes: 1) patients treated with a standardized steroid-free, calcineurin inhibitor sparing protocol (Clinical Islet Transplantation (CIT) protocol 07); 2) patients treated with the standardized immunosuppressive protocol as well as the immunosuppressive drug deoxyspergualin (CIT protocol 03); and 3) patients with functional kidney allografts (CIT protocol 06). These protocols were originally initiated by the University of Minnesota, Northwestern University, and the University of California, San Francisco as part of the CIT consortium. Moving forward, the administration of the three will separate for logistic reasons as per NIH directive and RFA-DK-09-501, but the sites will continue to share the knowledge, expertise, and protocols that were initiated during the first five years of the CIT. RELEVANCE (provided by applicant): The proposed clinical protocols outlined in this application are designed to: 1) examine the effects of peritransplant addition of the immunosuppressive agent deoxyspergualin to a standardized immunosuppressive regimen in pancreatic islet transplantation in type 1 diabetic recipients; and 2) examine the outcomes of pancreatic islet transplantation in type 1 diabetic recipients with kidney allografts. We believe that the results of these studies will improve the efficacy of islet transplantation and contribute to the transition of clinical islet transplantation from clinical research to clinical care.