ISLET TRANSPLANTATION IN KIDNEY TRANSPLANT RECIPIENTS W/TYPE 1 DIABETES

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。这项申请的目的是利用GCRC资源移植人胰岛(胰岛素产生细胞)，用于治疗患有肾衰竭并曾因糖尿病肾脏疾病接受过肾脏移植的1型糖尿病患者。从20世纪70年代初的S到2000年，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。胰岛移植作为一种1型糖尿病的治疗方法已经有了显着的改善，埃德蒙顿的艾伯塔大学报告了成功的结果，自2000年以来，世界各地的多个其他中心也紧随其后。这组患者在两个供体胰腺连续胰岛移植和随后使用白细胞介素2受体抗体Daclizumab、西罗莫司和小剂量他克莫司进行免疫抑制后，表现出一致的1型糖尿病逆转。埃德蒙顿方案的成功推动了由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)和由NIH(NCRR)资助的“胰岛细胞资源中心”(ICR)的开发，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，我们的实验室已经获得了美国国立卫生研究院批准的cGMP指导下的胰岛细胞分离，并已经进行了超过36个月的胰岛分离程序。我们已经启动了一项临床试验，以仿效埃德蒙顿方案作为评估胰岛移植功能和结果的标准(GCRC#1391)，现在计划扩大研究对象群体，包括已经在服用免疫抑制药物以维持先前肾脏移植的受试者。本研究的目的是在一项单中心试点研究中评估同种异体胰岛移植重建1型糖尿病患者稳定的血糖控制和稳定的肾移植功能的安全性和有效性。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，他们具有稳定的肾脏移植功能，并且正在服用与上述胰岛移植试验相同的药物。在移植后的头两年，将监测和记录不良事件。在移植后3个月及以后，将评估1型糖尿病同种异体胰岛移植受者中完全(胰岛素非依赖性和HbA1c及Lt；7%)和部分(胰岛素依赖，基础或刺激的C-肽水平大于或等于0.5 ng/ml，糖化血红蛋白小于或等于7%)胰岛移植功能的比例。

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.