TYPE 1 DIABETES TRIALNET PROTOCOL TN-05 / EFFECTS OF RITUXIMAB ON THE PROGRESS

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。子项目及 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。 该研究是一项双臂、多中心、随机、双盲、安慰剂对照临床试验，旨在评估利妥昔单抗（抗 CD20 单克隆抗体）治疗新发 1 型糖尿病患者的安全性、有效性和作用方式。两组受试者将接受标准的强化糖尿病治疗，包括胰岛素和饮食管理。 Rituximab（RITUXANR、Genetech 和 Biogen Idec）是一种嵌合鼠/人单克隆抗体，被批准用于治疗 B 细胞非霍奇金淋巴瘤。该抗体与 B 细胞表面的 CD20 抗原结合并介导 B 细胞耗竭。 随机分配接受利妥昔单抗治疗的参与者将每周接受四剂 375mg/m2 静脉注射。总研究持续时间约为 4 年（每个受试者 2 年受试者累积和 2 年随访）。对于那些在 2 年内β细胞功能持续存在和/或通过描述性分析可检测到治疗的免疫学效应的患者，将继续进行长达 4 年的随访，直到可检测到的 β 细胞功能消失或免疫学变化得到解决。 本研究要评估的主要统计假设是，使用利妥昔单抗的研究受试者的平均 C 肽值是否与一年随访时评估的安慰剂受试者的平均值存在显着差异。 次要目标 该研究将检查拟议治疗对免疫效应替代标志物的影响，即疾病特异性结果和免疫学结果。 主要纳入标准为：过去 3 个月内患有 1 型糖尿病，年龄 8-45 岁，且至少有一种糖尿病相关自身抗体。

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 study is a two-arm, multicenter, randomized, double masked, placebo-controlled clinical trial to assess the safety, efficacy, and mode of action of rituximab, anti-CD20 monoclonal antibody, for the treatment of individuals with new onset type 1 diabetes. Subjects in both arms will receive standard intensive diabetes treatment with insulin and dietary management. Rituximab (RITUXANR, Genetech and Biogen Idec) is a chimeric murine/human monoclonal antibody approved for the treatment of B cell non-Hodgkin's lymphoma. The antibody binds to the CD20 antigen on the surface of B cells and mediates B cell depletion. Participants randomly assigned to rituximab treatment will receive four doses of 375mg/m2 IV each a week apart. Total study duration is approximately 4 years (2 years subject accrual and 2 years follow-up per subject). Follow-up for up to 4 years will continue for those who have persistence of beta cell function at 2 years and/or detectable immunologic effects of treatment by descriptive analysis until the disappearance of detectable beta cell function or resolution of immunologic changes. The primary statistical hypothesis to be assessed in this study is whether the mean C-peptide value for study subjects on rituximab differs significantly from the mean value for placebo subjects assessed at one year of follow-up. Secondary Goals The study will examine the effect of the proposed treatment on surrogate markers for immunologic effects, namely disease-specific outcomes and immunological outcomes. Major inclusion criteria are: Type 1 diabetes within past 3 months, age 8-45 years, and at least one diabetes associated autoantibody.