ISLET TRANSPLANTATION IN TYPE 1 DIABETIC PATIENTS USING THE EDMONTON PROTOCOL

使用埃德蒙顿方案对 1 型糖尿病患者进行胰岛移植

• 批准号: 7603308
• 负责人: KENNETH S POLONSKY
• 金额: $ 0.11万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603308
• 关键词: Alberta province; Allografting; Antibodies; Antilymphocyte Globulin; Appendix; Azathioprine; Cell physiology; Complications of Diabetes Mellitus; Computer Retrieval of Information on Scientific Projects Database; Cyclosporine; Cyclosporins; Daclizumab; Diabetic Coma; Dose; Enrollment; Evaluation; Freedom; Funding; Glucocorticoids; Grant; Immunosuppression; Immunosuppressive Agents; Infusion procedures; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Interleukin 2 Receptor; Islet Cell; Islets of Langerhans; Islets of Langerhans Transplantation; Lipids; Metabolic Control; Minor; Monoclonal Antibodies; Organ Transplantation; Pancreas; Patients; Portal vein structure; Procedures; Protocols documentation; Publishing; Reporting; Reproducibility; Research; Research Personnel; Resources; Schedule; Series; Sirolimus; Source; Subjects Selections; Tacrolimus; Therapeutic immunosuppression; Training; Transplantation; Treatment Protocols; United States National Institutes of Health; Universities; Update; Visit; Week; blood glucose regulation; design; follow-up; islet; success; 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. 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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 胰岛移植已被研究作为 1 型糖尿病的治疗方法，对象是尽管接受胰岛素治疗但血糖控制不佳的选定患者。然而，人们一直希望这种方法能够长期摆脱对外源性胰岛素的需要，同时稳定糖尿病的继发并发症，但在实践中却未能实现。自 1990 年以来，在 267 例同种异体移植中，只有 12.4% 的患者能够实现胰岛素依赖超过一周，只有 8.2% 的患者能够实现胰岛素依赖超过一年。在大多数这些手术中，免疫抑制方案包括用抗淋巴细胞球蛋白联合环孢菌素、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。来自埃德蒙顿的一系列连续七名 1 型糖尿病受试者的研究表明，当无糖皮质激素的免疫抑制与输注足够的胰岛质量相结合时，胰岛移植可以导致胰岛素独立性和良好的代谢控制。在该系列中，所有七名受试者在经皮肝门静脉胰岛移植后很快就实现了持续的胰岛素独立。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才能实现持续的胰岛素独立。几乎所有供体胰腺在接受胰岛分离程序之前都因适合全器官移植而被拒绝。移植后没有再出现低血糖昏迷。 并发症很轻微，随访期间脂质浓度没有显着增加。 在本报告的更新中，共有 10 名连续受试者在进行胰岛细胞移植和使用不含糖皮质激素的免疫抑制方案（包括西罗莫司、低剂量他克莫司和针对白细胞介素 2 受体的单克隆抗体（达克珠单抗））后仍保持胰岛素独立。 这项多中心可行性研究旨在确定在单个中心（埃德蒙顿阿尔伯塔大学夏皮罗等人）取得的初步成功的可重复性。这将通过向参与中心提供培训和标准化标准以及受试者选择、尸体供体资格胰岛细胞处理、胰岛移植和移植后治疗方案的程序来确定。根据该协议，最多 10 个中心的总共 40 名受试者将被招募。随访时间预计在第二次（或最后一次）移植后持续 1 年，研究应持续约 2 年。随访和评估时间表见附件1。