ISLET TRANSPLANTATION IN KIDNEY TRANSPLANT RECIPIENTS W/TYPE 1 DIABETES

1 型糖尿病肾移植受者的胰岛移植

• 批准号: 7377843
• 负责人: ALEXANDER C WISEMAN
• 金额: $ 0.22万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7377843
• 关键词: ISLET; TRANSPLANTATION; KIDNEY; TRANSPLANT; RECIPIENTS

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 to transplant human pancreatic islets (insulin-producing cells) for the treatment of type 1 diabetes in patients who have kidney failure and have previously received a kidney transplant as a result of diabetic kidney disease. Islet transplants have been performed in nearly 400 patients with type1 diabetes from the early 1970's to 2000, 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 has dramatically improved with successes reported at the University of Alberta in Edmonton followed by multiple other centers around the world since the year 2000. This group demonstrated consistent reversal of Type1 diabetes following sequential islet transplantation from two donor pancreases and subsequent immunosuppression with the interlukin-2 receptor antibody daclizumab, sirolimus, and low-dose tacrolimus. 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) 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 cell isolation under cGMP guidelines and has performed 64 pancreatic islet isolation procedures over 36 months. We have initiated a clinical trial to emulate the Edmonton protocol as a standard from which to assess function and outcomes of islet transplantation (GCRC #1391) and now plan to expand the study subject population to include subjects who are already on immunosuppressive medications to sustain a previous kidney transplant. The objective of this study is to assess the safety and efficacy of islet allotransplantation for the re-establishment of stable blood sugar control in patients with type 1 diabetes and stable kidney transplant function in a single-center pilot study. Potential candidates for islet allotransplantation will include patients greater than or equal to 18 years of age with type 1 diabetes, who have had stable kidney transplant function, and who are on medications identical to the above-mentioned islet transplant trials. 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 HbA1c<7%) and partial (insulin dependence, basal or 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 3 months post transplant and beyond will be assessed.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。本申请的目的是利用GCRC资源移植人胰岛（产胰岛素细胞），用于治疗患有肾衰竭且之前因糖尿病肾病接受过肾移植的1型糖尿病患者。从20世纪70年代早期到2000年，已经在近400例1型糖尿病患者中进行了胰岛移植，但在“埃德蒙顿经验”之前，该队列中只有41例接受者在移植后实现了胰岛素依赖性。胰岛移植作为1型糖尿病的治疗方法已经有了显著的改善，自2000年以来，埃德蒙顿的阿尔伯塔大学报道了成功，随后世界各地的多个其他中心也报道了成功。这一组显示了从两个供体胰腺连续胰岛移植和随后的白细胞介素-2受体抗体daclizumab，西罗莫司和低剂量他克莫司免疫抑制后1型糖尿病的一致逆转。埃德蒙顿方案的成功激发了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10个中心，以模仿阿尔伯塔大学的方法）的建立，以及NIH（NCRR）资助的“胰岛细胞资源中心”（ICR）的发展，以优化每个胰腺的使用。我们的中心，科罗拉多大学健康科学中心，是10个被选为胰岛细胞资源中心的中心之一。目前，我们的实验室已获得NIH批准，根据cGMP指南进行胰岛细胞分离，并在36个月内进行了64次胰岛分离程序。我们已经启动了一项临床试验，以模仿埃德蒙顿方案作为评估胰岛移植功能和结局的标准（GCRC #1391），现在计划扩大研究受试者人群，纳入已经接受免疫抑制药物以维持既往肾移植的受试者。本研究的目的是在一项单中心初步研究中评估同种异体胰岛移植在1型糖尿病和稳定的肾移植功能患者中重建稳定血糖控制的安全性和有效性。胰岛同种异体移植的潜在候选者将包括大于或等于18岁的1型糖尿病患者，他们具有稳定的肾移植功能，并且正在接受与上述胰岛移植试验相同的药物治疗。将在移植后的头两年监测和记录不良事件。将评估在移植后3个月及以后具有完全（胰岛素非依赖性和HbA 1c <7%）和部分（胰岛素依赖性、基础或刺激的C肽水平大于或等于0.5ng/mL和糖化血红蛋白小于或等于7%）胰岛移植物功能的1型糖尿病胰岛移植物接受者的比例。