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）： 胰岛移植是一个有趣的治疗平台，用于治疗T1D，但不会成为广泛的临床现实，直到可以证明胰岛产品可以在有效的方式始终如一地提供一致的治疗益处。为了应对这些挑战，形成了临床胰岛移植（CIT）财团。延续奖的目的是完成现有的CIT胰岛移植研究，以实质上改善对T1D的处理并获得人类胰岛产品的许可。已经制定了三个研究方案。与每种方案相关的具体目的是：1。确定脱氧胰蛋白酶（DSG）对T1D患者胰岛移植的植入和功能的移植周期施用的安全性和功效（CIT方案03）。 2。为了确定接受胰岛移植的T1D患者中无类固醇，克莫司免疫抑制方案的安全性和功效（CIT方案07）。 3。确定胰岛移植在T1D肾脏同种异体移植受体中的疗效（CIT方案06）。为了实现CIT-03的目的，西北地区将参加一项前瞻性，随机，三中心的开放标签试验，该试验评估了DSG对移植后胰岛功能的安全性和功效，这是长期存在的TID，这是对密集型胰岛素治疗的难治性。研究中的三个中心。西北，明尼苏达州和UCSF将使用DSG（CLT-03）共同移植20名受体，并将48名受体中的12个贡献为CIT-07协议，该协议是注册试验组件，也是DSG研究的对照组。西北至少将在CIT-03/-07中移植10-11名受试者，在CIT-06中将4例移植。为了加快这些试验的完成，西北航空的目标是在当前赠款裁决颁布之前，根据CLT-03和2个受试者根据CLT-03和2受试者进行第4名受试者。 Northwestern使用CIT批次记录符合CIT联盟的资格标准，以获得优质的胰岛隔离标准，并根据活动量和质量结果的临床经验。已经实现了现场激活。迄今为止，西北已经移植了3例患者，全部随机分配给CLT-03研究。西北航空的积极参与者在CIT临床试验中的积极参与者处于良好状态。 相关性（由申请人提供）：1型糖尿病（T1D）在美国遭受了近200万人的困扰，其中大多数是儿童或年轻人，并且未经治疗，这是一种致命的疾病。可以进行胰岛素治疗，但不会导致与健康相关的生活质量，并可能导致糖尿病性视网膜病变和肾病，这是成人失明和肾脏移植的最常见原因。目的是实现具有胰岛移植的1型糖尿病患者的胰岛素独立性，改善其整体生活质量和疾病管理的风险比整个胰腺移植较少。