ISLET TRANSPLANTATION FOR TYPE 1 DIABETES

1 型糖尿病的胰岛移植

• 批准号: 7719449
• 负责人: ALEXANDER C WISEMAN
• 金额: $ 0.11万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7719449
• 关键词: Adverse effects; Adverse event; Age-Years; Alberta province; Arginine; Awareness; C-Peptide; Caring; Clinical; Clinical Trials; Colorado; Computer Retrieval of Information on Scientific Projects Database; Cyclic GMP; Daclizumab; Dependence; Development; Diabetes Mellitus; Dose; Fc Receptor; Foundations; Funding; Glycosylated Hemoglobin; Grant; Guidelines; Health Sciences; Human; Hypoglycemia; Immune Tolerance; Immunosuppression; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Islets of Langerhans Transplantation; Label; Laboratories; Metabolic; Methodology; Monitor; National Center for Research Resources; Outcome; Pancreas; Patients; Population; Preparation; Procedures; Protocols documentation; Reporting; Research; Research Personnel; Resources; Safety; Sirolimus; Source; Standards of Weights and Measures; Steroids; Tacrolimus; Therapeutic immunosuppression; Titrations; Transplantation; Treatment Protocols; United States National Institutes of Health; Universities; cohort; experience; glycemic control; graft function; islet; islet allograft; novel; pilot trial; success; transplantation typing; type I diabetic

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The objective of this application is to utilize GCRC resources for use of freshly isolated human pancreatic islets for the treatment of type 1 diabetes. Islet allografts have been performed in nearly 400 patients with type1 diabetes since the early 1970's, but prior to the "Edmonton experience", only forty-one recipients of this cohort had achieved insulin independence following transplantation. Islet transplantation as a treatment for type1 diabetes took a dramatic step forward with successes reported at the University of Alberta in Edmonton. This group demonstrated consistent reversal of Type1 diabetes following sequential islet transplantation from two donor pancreases and subsequent immunosuppression with a novel, steroid-free regimen including interlukin-2 receptor antibody daclizumab, sirolimus, and low-dose tacrolimus. The rationale behind the Edmonton approach had been to maximize the potential for insulin by titration of an adequate islet transplant mass so that the potential side effects of immunosupression are outweighed by the benefits of insulin independence and tight glycemic control. The success of the Edmonton Protocol has provoked the creation of an NIH-funded clinical trial (the Immune Tolerance Network Islet Transplant Trial enlisting 10 centers worldwide to emulate the methodology of the U of Alberta),the development of Islet Transplant Centers funded by the Juvenile Diabetes Research Foundation, and the development of "Islet Cell Resource Centers" (ICRs) funded by the NIH (NCRR) to optimize the use of each pancreas for potential transplant. Our center, the University of Colorado Health Sciences Center, was one of 10 centers selected for participation as an Islet Cell Resource Center. At present, our laboratory has gained NIH approval for islet isolation under cGMP guidelines and has performed 41 pancreatic islet isolation procedures over 18 months. Our facility is now prepared to move toward clinical use of our human islet preparations. We plan to emulate the Edmonton protocol as a standard from which to assess function and outcomes of islet transplantation prior to transitioning to novel treatment protocols and patient populations. The objective of this study is to assess the safety and efficacy of islet allotransplantation for the re-establishment of stable glycemic control in patients with type 1 diabetes in an open-label, single-center pilot trial. Potential candidates for islet allotransplantation will include patients greater than or equal to 18 years of age with type 1 diabetes in whom metabolic liability/instability, reduced awareness of hypoglycemia, progressive secondary complications despite intensive management, in cooperation with their diabetes care team. Adverse events will be monitored and recorded throughout the first two years post-transplant. The proportion of type 1 diabetic islet allograft recipients with full (insulin independence and HbA1c7%) and partial (insulin dependence, basal or arginine-stimulated C-peptide levels of greater or equal to 0.5ng/mL and glycated hemoglobin less than or equal to 7%) islet graft function at one year post transplant and beyond will be assessed.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 本申请的目的是利用GCRC资源将新鲜分离的人胰岛用于1型糖尿病的治疗。自20世纪70年代初S以来，近400名1型糖尿病患者接受了胰岛移植，但在“埃德蒙顿经验”之前，这一队列中只有41名受者在移植后实现了胰岛素独立。艾伯塔大学埃德蒙顿分校报道，胰岛移植作为1型糖尿病的治疗方法向前迈出了戏剧性的一步。这组患者在两个供体胰腺连续胰岛移植和随后的免疫抑制后，表现出一致的1型糖尿病逆转，该免疫抑制方案包括白细胞介素2受体抗体Daclizumab、西罗莫司和小剂量他克莫司。Edmonton方法背后的基本原理是通过滴定足够的胰岛移植质量来最大限度地发挥胰岛素的潜力，以便免疫抑制的潜在副作用被胰岛素独立和严格控制血糖的好处所抵消。埃德蒙顿协议的成功促成了由NIH资助的临床试验(免疫耐受网络胰岛移植试验在全球招募了10个中心，以效仿艾伯塔大学的方法)，由青少年糖尿病研究基金会资助的胰岛移植中心的发展，以及由NIH(NCRR)资助的“胰岛细胞资源中心”(ICRS)的发展，以优化每个胰腺的使用，以进行潜在的移植。我们的中心，科罗拉多大学健康科学中心，是被选为胰岛细胞资源中心的10个中心之一。目前，我们的实验室已经根据cGMP指南获得了NIH对胰岛分离的批准，并在18个月内进行了41次胰岛分离手术。我们的设施现在准备将我们的人类胰岛制剂应用于临床。我们计划仿效埃德蒙顿方案，作为在过渡到新的治疗方案和患者群体之前评估胰岛移植的功能和结果的标准。本研究的目的是在一项开放标签的单中心先导试验中，评估同种异体胰岛移植重建1型糖尿病患者稳定血糖控制的安全性和有效性。同种异体胰岛移植的潜在候选者将包括年龄大于或等于18岁的1型糖尿病患者，这些患者与他们的糖尿病护理团队合作，代谢易感性/不稳定性，对低血糖的认识降低，尽管进行了密集的治疗，但仍出现进行性继发性并发症。在移植后的头两年，将监测和记录不良事件。在移植后一年及以后，将评估1型糖尿病同种异体胰岛移植受者完全(胰岛素非依赖性和HbA1c7%)和部分(胰岛素依赖，基础或精氨酸刺激的C-肽水平大于或等于0.5 ng/毫升，糖化血红蛋白小于或等于7%)胰岛移植功能的比例。