Clinical Islet Transplantation at Northwestern

西北大学临床胰岛移植

• 批准号: 7791909
• 负责人: Dixon B Kaufman
• 金额: $ 161.88万
• 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/7791909
• 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 的一个有趣的治疗平台，但只有在能够证明胰岛产品能够以有效的方式、一致的基础上安全地提供实质性的治疗益处之前，它才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) 联盟成立了。继续奖的目的是完成现有的 CIT 胰岛移植研究，以大幅改善 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。与每个方案相关的具体目标是： 1. 确定移植前后给予脱氧精胍菌素 (DSG) 对 T1D 患者胰岛移植物的植入和功能的安全性和有效性（CIT 方案 03）。 2. 确定接受胰岛移植的 T1D 患者中无类固醇、不使用他克莫司的免疫抑制方案的安全性和有效性（CIT 方案 07）。 3. 确定胰岛移植对 T1D 肾同种异体移植受者的疗效（CIT 方案 06）。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 对患有长期 TID 且难治性 TID 受试者的移植后胰岛功能的安全性和有效性。强化胰岛素治疗。研究的三个中心。西北大学、明尼苏达州和加州大学旧金山分校将使用 DSG (ClT-03) 共同移植 20 名受者，并将 48 名受者中的 12 名贡献到 CIT-07 方案中，该方案是注册试验的组成部分，也作为 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 中移植至少 4 名患者。为了加快完成这些试验，西北大学的目标是在当前拨款结束之前移植 ClT-03 下的 4 名受试者和 ClT-07 下的 2 名受试者。 Northwestern 已满足 CIT 联盟现场资格标准，即使用 CIT 批次记录的优质胰岛隔离标准，以及基于活动量和质量结果的临床经验。站点激活已实现。迄今为止，西北大学已移植了 3 名患者，全部随机参加 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）：在美国，1 型糖尿病 (T1D) 困扰着近 200 万人，其中大多数是儿童或年轻人，如果未经治疗，它是一种致命的疾病。可以进行胰岛素治疗，但不会带来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。目标是通过胰岛移植实现 1 型糖尿病患者的胰岛素独立，提高他们的整体生活质量和疾病管理，且风险低于全胰腺移植。