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

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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CD 20单克隆抗体）治疗新发1型糖尿病患者的安全性、疗效和作用方式。两组中的受试者将接受胰岛素和饮食管理的标准强化糖尿病治疗。利妥昔单抗（RITUXANR，Genetech和Biogen Idec）是一种嵌合鼠/人单克隆抗体，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CD 20抗原结合并介导B细胞耗竭。 随机分配至利妥昔单抗治疗组的受试者将接受4次375 mg/m2 IV给药，每次间隔一周。总研究持续时间约为4年（2年受试者入组和2年随访每例受试者）。对于2年时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，直至可检测到的β细胞功能消失或免疫学变化消退。 本研究中评估的主要统计假设是接受利妥昔单抗治疗的研究受试者的平均C肽值是否与安慰剂受试者在一年随访时评估的平均值显著不同。 次要目的本研究将检查所提出的治疗对免疫学效应的替代标志物的影响，即疾病特异性结局和免疫学结局。 主要入选标准为：过去3个月内患有1型糖尿病，年龄8-45岁，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.