Clinical Islet Transplantation at Northwestern

西北大学临床胰岛移植

• 批准号: 7941899
• 负责人: Xunrong Luo
• 金额: $ 127.46万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7941899
• 关键词: Address; Adult; Anti-Inflammatory Agents; Award; Blindness; Child; Clinical; Clinical Trials; Control Groups; Development; Diabetic Retinopathy; Disease; Disease Management; Engraftment; Fostering; Goals; Grant; Gusperimus; Human; Immunosuppressive Agents; Insulin; Insulin-Dependent Diabetes Mellitus; Islets of Langerhans; Islets of Langerhans Transplantation; Kidney Diseases; Kidney Transplantation; Lead; Licensure; Minnesota; National Institute of Allergy and Infectious Disease; National Institute of Diabetes and Digestive and Kidney Diseases; Outcome; Pancreas; Participant; Patients; Positioning Attribute; Protocols documentation; Quality of life; Randomized; Refractory; Risk; Safety; Site; Steroids; Tacrolimus; Therapeutic; Transplantation; United States; United States National Institutes of Health; base; diabetic patient; experience; health related quality of life; improved; islet; kidney allograft; meetings; open label; pancreatic islet function; prospective; type I diabetic; young adult

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.

描述(由申请人提供)： 胰岛移植是治疗T1D的一个耐人寻味的治疗平台，但在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，不会成为广泛的临床现实。为了应对这些挑战，临床胰岛移植(CIT)联盟应运而生。继续奖的目的是完成现有的CIT胰岛移植研究，以显著改善T1D的治疗并获得人类胰岛产品的许可。已经制定了三项研究方案。每个方案的具体目标是：1.确定围移植期应用脱氧精灵(DSG)对T1D患者胰岛移植的安全性和有效性(CIT方案03)。2.确定在接受胰岛移植的T1D患者中使用非类固醇、非他克莫司的免疫抑制方案的安全性和有效性(CIT协议07)。3.探讨同种异体T1D肾移植患者胰岛移植的疗效。为了实现CIT-03的目标，西北大学将参与一项前瞻性、随机、三中心、开放标签试验，评估DSG对长期存在的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移植20名使用DSG(CLT-03)的接受者，并将48名接受者中的12人加入CIT-07方案，这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名受试者，在CIT-06中移植4名患者。为了加快完成这些试验，西北大学的目标是在目前的拨款结束之前，在CLT-03下移植4名受试者，在CLT-07下移植2名受试者。西北大学已经使用CIT批次记录满足了CIT联盟的质量胰岛分离标准以及基于活动量和质量结果的临床经验的现场资格标准。已经实现了站点激活。到目前为止，西北大学已经移植了3名患者，他们都随机参加了CLT-03研究。西北大学处于有利地位，将继续作为CIT临床试验的积极参与者。 相关性(由申请人提供)：1型糖尿病(T1D)在美国困扰着近200万人，其中大多数是儿童或年轻人，如果不治疗，它是一种致命的疾病。可以进行胰岛素治疗，但不会产生与健康相关的良好生活质量，还可能导致糖尿病视网膜病变和肾病，这两种疾病分别是导致成人失明和肾脏移植的最常见原因。其目标是使接受胰岛移植的1型糖尿病患者实现胰岛素独立，以比全胰腺移植更低的风险改善他们的整体生活质量和疾病管理。