HOKT3γ1 (ALA-ALA), SIROLIMUS AND LOW DOSE TACROLIMUS THERAPY IN TYPE 1 DIAB

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。 这是一项前瞻性开放研究，研究对象为首次接受胰岛移植的10名1型糖尿病患者。所有参与者都将接受hOKT3；1(ALA-ALA)和利妥昔单抗的诱导免疫治疗。维持性免疫抑制将与西罗莫司和逐渐减少的小剂量他克莫司一起使用。主要终点检查利用hOKT3&1(ALA-ALA)和利妥昔单抗，西罗莫司和临时他克莫司维持免疫抑制在逆转1到2个门脉内同种异体胰岛移植后糖尿病和维持移植胰岛针对同种异体免疫和自身免疫的充分免疫保护方面的有效性。更具体地说，主要终点检查在最初的胰岛移植一年后完全具有胰岛移植功能的受试者的比例(胰岛素独立性；HbA1c 6.5%；没有发生严重低血糖)。次要终点检查方案的安全性，即与免疫抑制相关的程序并发症和不良事件的发生，特别强调在胰岛移植后1年恶性肿瘤、机会性感染和其他细菌、真菌和病毒感染的累积发生率。

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. This is a prospective, open-label study in 10 type 1 diabetic participants receiving their first islet-only transplant. All participants will receive induction immunotherapy with hOKT3γ1 (Ala-Ala), and rituximab. Maintenance immunosuppresion will be with sirolimus and tapered, low dose tacrolimus. The primary endpoint examines the efficacy of utilizing hOKT3γ1 (Ala-Ala), and rituximab, induction with sirolimus and temporary tacrolimus maintenance immunosuppresion in reversing diabetes following 1 to 2 intraportal islet allotransplants and in maintaining adequate immunological protection of transplanted islets against both allo- and autoimmunity. More specifically, the primary endpoint examines the proportion of subjects with full islet transplant function (insulin independence; HbA1c 6.5% ; and no episodes of severe hypoglycemia) at 1 year after the initial islet transplant. The secondary endpoint examines the safety of the regimen, i.e., the occurence of procedural complications and adverse events related to immunosuppressive, with particular emphasis on the cumulative incidence of malignancies, opportunistic infections, and other bacterial, fungal , and viral infections at 1 year after the islet transplant.