PHASE I/II TRIAL TETRATHIOMOLYBDATE (TM) IN PTS W/ USUAL INTERSTITIAL PNEUMONIA

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。普通型间质性肺炎(UIP)是一种肺纤维化，与肺的疤痕形成有关，通常是致命的。平均生存期为确诊后2~4年。血管生成，即生长新血管的能力，被认为是UIP典型的纤维化反应所必需的关键成分。四硫钼酸(TM)是一种为治疗威尔逊氏病(一种影响肝脏的铜质疾病)而开发的抗铜药物。TM还通过降低全身铜水平，在患有癌症的非威尔逊病患者以及动物肿瘤模型中产生抗血管生成作用。TM在uIP中试验的理论基础来自于它在博莱霉素小鼠肺纤维化模型中的成功应用，以及它的抗纤维化、抗炎和抗血管生成特性。这项针对先前治疗失败的UIP患者的开放标签研究将每隔三个月跟踪患者一年。在每次就诊时，将进行肺功能研究和生活质量问卷调查。在基线和治疗12个月后，将进行高分辨率CT扫描(一种X光)和6分钟步行试验。TM将口服，剂量将被滴定以抑制血管生成，而不会因铜缺乏而造成毒性。最初将每周监测一次，然后适当时每两周和每月监测一次。主要终点是治疗12个月后肺功能的变化。研究记录将保存在一个受密码保护的数据库中，只有研究调查人员才能访问。书面文件将保存在上了锁的自习室的患者活页夹中。患者将书面知情同意参与这项研究。

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. Usual interstitial pneumonia (UIP) is a type of pulmonary fibrosis that is associated with scarring of the lung and is often fatal. The average survival is 2-4 years from the time of diagnosis. Angiogenesis, the ability to grow new blood vessels, is believed to be a key component required for the fibrotic response typical of UIP. Tetrathiomolybdate (TM) is an anticopper drug developed for the treatment of Wilson's disease (a copper disorder that affects the liver). TM also produces an antiangiogenic effect in non-Wilson's disease patients with cancer, and in animal tumor models, by lowering systemic copper levels. The rationale for a trial of TM in UIP stems from its successful use in the bleomycin mouse model of pulmonary fibrosis, and its antifibrotic, antiinflammatory, antiangiogenic properties. This open-label study for patients with UIP that have failed previous treatment will follow patients for one year at three-month intervals. At each of the visits pulmonary function studies and quality of life questionnaires will be performed. A high resolution CT scan (a type of x-ray) and a six minute walk test will be performed at baseline as well as after 12 months of therapy. TM will be given orally and the dose will be titrated to inhibit angiogenesis without causing toxicity from copper deficiency. Patients will be monitored weekly initially and then biweekly and monthly if appropriate. The primary endpoint is change in pulmonary function after 12 months of therapy. Research records will be kept in a password protected database accessible only by study investigators. Written documents will be kept in patient binders in a locked study office. Patients will give written informed consent to participate in this study.