PREVENTION OF DIABETES PROGRESSION TRIAL (PDPT)

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。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。所列机构为中心机构，不一定是研究者机构。如果在B细胞破坏之前调节I型糖尿病中由1型辅助性T细胞（Th 1）及其分泌的细胞因子（包括IFN-γ、TNF-α和IL-2）介导的自身免疫应答，则可能预防胰岛素缺乏。Daclizumab（Zenapax）是一种对IL-2受体具有特异性的人源化IgG 1单克隆抗体，具有受体拮抗剂的功能。其20天的半衰期允许每2-3周IV给药一次。Daclizumab被批准用于预防急性肾移植排斥反应。通过3年随访的全身输注反应、肾毒性、感染或恶性肿瘤的发生率测量，未证明有毒性。我们提出了一项开放标签试验，以测试达利珠单抗在部分残留B细胞功能的儿童中的安全性和有效性。100名1-16岁的儿童将被招募到为期两年的试验中，并随机接受常规治疗或常规治疗与daclizumab联合治疗。将通过蜜月期持续时间、胰岛素剂量、HgA 1C、糖化白蛋白水平、C肽水平、空腹胰岛素/葡萄糖比值和IVGTT评估疗效。免疫学疗效将包括评估外周血、胰岛细胞、胰岛素和GAD抗体中的CD 25表达，以及体外T细胞对GAD的增殖反应。将通过评估输注相关毒性、感染的频率和类型、达克珠单抗抗体的产生以及化学和血液学特征来监测安全性。如果在6个月内未表现出临床应答，则将停用达克珠单抗，但将在研究期间监测疗效和安全性参数。

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. If the Autoimmune response in Type I diabetes, mediated by T-helper Type 1 (Th1) cells and their secreted cytokines including IFN-y, TNF-a and IL-2, could be modulated prior to B cell destruction, insulin deficiency might be prevented. Daclizumab (Zenapax), a humanized IgG1 monoclonal antibody specific for IL-2 receptor, functions as a receptor antagonist. Its 20 day half-life permits IV drug dosing every 2-3 weeks. Daclizumab is approved for prevention of acute renal allograft rejections. No toxicity has been demonstrated as measured by rates of systemic infusion reaction, nephrotoxicity, infections, or malignancies with three years of follow-up. We propose an open label trial to test the safety and efficacy of daclizumab in children with partial residual B cell function. One hundred children, ages 1-16 years, will be recruited into the two year trial and randomized either to conventional therapy or conventional treatment in combination with daclizumab. Efficacy will be assessed by duration of the honeymoon period, dose of insulin, HgA1C, glycated albumin levels, C-peptide levels, fasting insulin to glucose ratios and IVGTT. Immunologic efficacy will include assessment of CD25 expression in peripheral blood, islet cell, insulin and GAD antibodies, and in vitro T cell proliferative response to GAD. Safety will be monitored by assessing infusion-related toxicities, frequency and type of infections, development of daclizumab antibodies, and chemistry and hematological profiles. If a clinical response is not demonstrated by 6 months, daclizumab will be discontinued, but efficacy and safety parameters will be monitored for the duration of the study.