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。 这项研究是一项双臂、多中心、随机、双掩蔽、安慰剂对照的临床试验，旨在评估抗CD20单抗利妥昔单抗治疗新发1型糖尿病患者的安全性、有效性和作用方式。两组受试者都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 and Biogen IDEC)是一种鼠/人嵌合单抗，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细胞的耗竭。随机分配到利妥昔单抗治疗的参与者将每周接受四次375 mg/m2的静脉注射。总研究持续时间约为4年(每名研究对象应计2年，随访2年)。对于那些持续2年的β细胞功能和/或通过描述性分析检测到治疗的免疫效果的患者，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变化消失。在这项研究中要评估的主要统计假设是，服用利妥昔单抗的研究对象的平均C-肽值是否与安慰剂受试者在一年随访时评估的平均值有显著差异。次要目标本研究将检查拟议治疗对免疫效果的替代标记物的影响，即疾病特异性结果和免疫学结果。主要纳入标准是：过去3个月内患1型糖尿病，年龄8-45岁，以及至少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.