A PILOT STUDY OF EFFICACY OF ISLET TRANSPLANTATION IN TYPE I DIABETES

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。据估计，美国I型糖尿病的患病率约为80万人。目前尚无彻底的预防或治疗措施。胰岛移植是安全的，但直到最近，在改善I型糖尿病方面还没有常规有效。加拿大埃德蒙顿的阿尔伯塔大学最近在使用免疫抑制方案西罗莫司、他克莫司和IV zenapax的胰岛细胞移植方面取得了成功，不使用皮质类固醇。这些药物通常用于移植。埃德蒙顿的研究表明，为了实现胰岛素独立，需要两个供体胰腺。患者在第二次胰岛细胞移植前免疫抑制不到12周。目前尚不清楚，如果患者在再次移植前免疫抑制时间较长，是否会从一个供体胰腺获得胰岛素独立性。胰岛细胞的数量可能不是移植成功的决定因素。这项研究建立在埃德蒙顿经验的优势之上。该方法是将胰岛细胞移植到我们的肾移植人群中已经免疫抑制的I型糖尿病患者。这些患者在胰岛细胞移植前一直使用稳定的免疫抑制方案他克莫司和西罗莫司，不使用皮质类固醇。这项可行性研究将限制在5例患者，将在胰岛移植后随访至少一年。要观察的最重要的终点将是这些目前免疫抑制的患者在胰岛移植后胰岛素独立的频率和持续时间。

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 prevalence of type I diabetes in the U.S. is estimated to be about 800,000 individuals. There are no thoroughly preventative or curative measures currently available. Islet transplantation is safe, but until recently, has not been routinely effective in ameliorating type I diabetes. The University of Alberta in Edmonton, Canada has had recent success with islet cell transplantation using the immunousuppression regimen of sirolimus, tacrolimus and IV zenapax, without corticosteroids. These agents are commonly used in transplantation. The Edmonton study revealed the need for two donor pancreases in order to achieve insulin independence. Patients were immunosuppressed for less than twelve weeks prior to their second islet cell transplant. It is unclear whether insulin independence would have been achieved from one donor pancreas had the patients been immunosuppressed for a longer duration prior to retransplantation. The mass of islet cells may not be the determining factor for successful transplantation. This study builds on the strengths of the Edmonton experience. The approach is to perform islet cell transplants into type I diabetic patients from our kidney transplant population that are already immunosuppressed. These patients have been on a stable immunosuppression regimen of tacrolimus and sirolimus without corticosteroids prior to islet cell transplantation. This feasibility study will limit accrual to five patients that will be followed for at least one year post islet transplantation. The most important endpoint to be observed will be the frequency and duration of insulin-independence following islet transplantation in these currently immunosuppressed patients.