Clinical Islet Transplantation at Northwestern

描述（由申请人提供）： 胰岛移植是治疗T1 D的一个有趣的治疗平台，但在能够证明胰岛产品能够以有效的方式在一致的基础上安全地提供实质性的治疗益处之前，胰岛移植不会成为广泛的临床现实。为了应对这些挑战，成立了临床胰岛移植（CIT）联盟。延续奖的目的是完成现有的CIT胰岛移植研究，以大幅改善T1 D的治疗，并获得人类胰岛产品的许可证。已经制定了三项研究方案。具体目标，因为他们涉及到每一个协议是：1。确定T1 D患者中移植围术期给予脱氧精胍菌素（DSG）对胰岛移植物植入和功能的安全性和有效性（CIT方案03）。2.在接受胰岛移植的T1 D患者中确定无类固醇、他克莫司保留免疫抑制方案的安全性和有效性（CIT方案07）。3.确定胰岛移植在T1 D肾移植受者中的疗效（CIT方案06）。为了实现CIT-03的目标，西北大学将参加一项前瞻性、随机、三中心、开放标签试验，评估DSG对长期TID患者移植后胰岛功能的安全性和有效性，这些患者对强化胰岛素治疗无效。研究中的三个中心。西北大学、明尼苏达大学和加州大学旧金山分校将共同使用DSG（ClT-03）移植20名受体，并将48名受体中的12名纳入CIT-07方案，该方案是注册试验的组成部分，也是DSG研究的对照组。西北大学将在CIT-03/-07中移植至少10-11例受试者，在CIT-06中移植4例患者。为了加快这些试验的完成，西北大学的目标是在目前的赠款结束之前，根据ClT-03移植4名受试者，根据ClT-07移植2名受试者。Northwestern符合CIT联盟使用CIT批记录的优质胰岛分离标准的现场资格标准，以及基于活动量和质量结果的临床经验。已实现站点激活。到目前为止，西北大学已经移植了3名患者，全部随机分配到ClT-03研究。西北大学有能力继续积极参与CIT临床试验。 相关性（由申请人提供）：1型糖尿病（T1 D）困扰着美国近200万人，其中大多数是儿童或年轻人，未经治疗，这是一种致命的疾病。胰岛素治疗可以给药，但不能产生良好的健康相关生活质量，并可能导致糖尿病视网膜病变和肾病，这分别是成人失明和肾移植的最常见原因。目标是实现胰岛移植的1型糖尿病患者的胰岛素依赖性，改善他们的整体生活质量和疾病管理，风险低于全胰腺移植。

DESCRIPTION (provided by applicant): Islet transplantation is an intriguing therapeutic platform for treatment of T1D but will not become a widespread clinical reality until it can be proven that the islet product can safely provide a substantial therapeutic benefit on a consistent basis in an efficient manner. To address these challenges the Clinical Islet Transplant (CIT) Consortium was formed. The aim of the Continuation Award is to complete the existing CIT islet transplant studies to substantially improve treatment of T1D and obtain licensure of the human islet product. Three study protocols have been developed. The Specific Aims as they relate to each protocol are: 1. To determine the safety and efficacy of peri-transplant administration of deoxyspergualin (DSG) on the engraftment and function of pancreatic islet transplants in T1D patients (CIT Protocol 03). 2. To determine the safety and efficacy of a steroid-free, tacrolimus sparing immunosuppressive protocol in T1D patients receiving pancreatic islet transplants (CIT Protocol 07). 3. To determine the efficacy of islet transplantation in T1D kidney allograft recipients (CIT Protocol 06). To achieve the aims of CIT-03, Northwestern will participate in a prospective, randomized, three-center, open-label trial assessing the safety and efficacy of DSG on post-transplant islet function in subjects with long-standing TID that is refractory to intensive insulin therapy. The three centers in the study. Northwestern, Minnesota and UCSF, will collectively transplant 20 recipients using DSG (ClT-03) and contribute 12 of the 48 recipients into the CIT-07 protocol that is the registration trial component and also serves as the control group for the DSG study. Northwestern will transplant a minimum of 10-11 subjects in CIT-03/-07, and 4 patients in CIT-06. To expedite the completion of these trials, Northwestern aims to transplant 4 subjects under ClT-03 and 2 subjects under ClT-07 before the conclusion of the current grant award. Northwestern has met the CIT consortium site qualification criteria for quality islet isolation standards using the CIT batch record, and for clinical experience based on volume of activity and quality outcomes. Site activation has been achieved. To date, Northwestern has transplanted 3 patients, all randomized to the ClT-03 study. Northwestern is well positioned to continue as an active participant in the CIT clinical trials. RELEVANCE (provided by the applicant): Type 1 diabetes (T1D) afflicts nearly 2 million people in the United States, most of them children or young adults, and untreated, it is a fatal disease. Insulin therapy can be administered, but does not result in good health-related quality of life and can lead to diabetic retinopathy and nephropathy, which are the most common causes of adult blindness and kidney transplant respectively. The goal is to achieve insulin independence for Type 1 diabetes patients with Islet Transplantation, improving their overall quality of life and disease management with less risk than whole pancreas transplant.