ISLET TRANSPLANTATION IN TYPE 1 DIABETIC PATIENTS USING THE EDMONTON PROTOCOL

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。 胰岛移植已被研究为一种治疗1型糖尿病的方法，尽管有胰岛素治疗，但选择了血糖控制不足的患者。然而，这种方法将导致长期不需要外源性胰岛素，并稳定糖尿病继发性并发症的长期希望在实践中未能实现。自1990年以来移植的267例同种异体移植物中，只有12.4%的移植物胰岛素依赖超过一周，只有8.2%的同种异体移植物的胰岛素依赖时间超过一年。在大多数治疗过程中，免疫抑制方案包括用抗淋巴细胞球蛋白联合环孢素、硫唑嘌呤和糖皮质激素诱导抗体。 夏皮罗等人发表的观察结果。来自埃德蒙顿的来自一系列连续7名1型糖尿病受试者的研究表明，当不含糖皮质激素的免疫抑制与输入足够的胰岛质量相结合时，胰岛移植可以通过出色的代谢控制导致胰岛素独立。在这一系列研究中，所有7名受试者在经皮肝穿门静脉胰岛移植后均迅速获得持续的胰岛素依赖性。所有受者都需要来自两个供体胰腺的胰岛，其中一个需要来自两个供体的第三次移植，以实现持续的胰岛素独立。几乎所有的供体胰腺在接受胰岛隔离手术之前都被认为适合整个器官移植而被排斥。移植后没有发生进一步的低血糖昏迷。并发症很小，在随访期间，血脂浓度没有明显增加。在这篇发表的报告的更新中，共有10名连续的受试者在胰岛细胞移植和使用无糖皮质激素免疫抑制方案后保持胰岛素独立，该方案包括西罗莫司、小剂量他克莫司和抗白细胞介素2受体的单抗(Daclizumab)。 这项多中心可行性研究旨在确定在单一中心(艾伯塔大学埃德蒙顿分校的Shapiro等人)取得的初步成功的可重复性。这将通过为参与的中心提供培训和标准化的标准和程序来确定，这些标准和程序涉及主题选择、身体供体资格、胰岛细胞处理、胰岛移植和移植后治疗方案。根据这项协议，多达10个中心的40名受试者将被登记。第二次(或最后一次)移植后的随访持续时间为1年，研究应持续约2年。后续访问和评价的时间表见附录1。

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. Islet transplantation has been investigated as a treatment for Type 1 diabetes mellitus in selected patients with inadequate glucose control despite insulin therapy. However, the perennial hope that such an approach would result in long-term freedom from the need for exogenous insulin, with stabilization of the secondary complications of diabetes, has failed to materialize in practice. Of the 267 allografts transplanted since 1990, only 12.4% have resulted in insulin independence for periods of more than one week, and only 8.2% have done os for periods of more than one year. In the majority of these precedures, the regimen of immunosuppression consisted of antibody induction with an antilymphocyte globulin combined with cyclosporine, azathioprine, and glucocorticoids. The published observationd by Shapiro, et al. from Edmonton, from a series of seven consecutive subjects with Type 1 diabetes, indicate that islet transplantation can result in insulin independence with excelent metabolic control when glucocorticoid-free immunosuppression is combined with the infusion of an adequate islet mass. In that series, all seven subjects quickly attained sustained insulin independence after percutaneous transhepatic portal vein transplantation of islets. All recipients required islets form two donor pancreases, and one required a 3rd transplant from two donors to achieve sustained insulin independence. Nearly all donor pancreata were previously rejected as suitable for whole organ transplant before being subject to the islet isolation procedures. There were no further episodes of hypoglycemic coma following transplant. Complications were minor, and there were no significant increases in lipid concentrations during follow-up. In an update to this published report, a total of 10 consecutive subjects have now remained insulin independent following islet cell transplant and use of a glucocorticoid-free immunosuppressive protocol that includes sirolimus, low-dose tacrolimus, and a monoclonal antibody against the interleukin-2 receptor (daclizumab). This multi-center feasiblity study is designed to determine the reproducibility of the preliminary success obtained at a single center (Shapiro, et al., University of Alberta in Edmonton). This will be determined by provideing the participated centers with training and standardized criteria and procedures for subject selection, cadaveric donor qualifications islet cell processing, islet transplantation, and post-transplant treatment regimens. A total of 40 subjects at up to 10 centers are to be enrolled under this protocol. The duration of follow-up is intended to last for 1 year after the second (or final) transplant and the study should last about 2 years. The schedule of follow-up visits and evaluations is shown in Appendix 1.