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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。通常间质性肺炎（UIP）是一种与肺瘢痕相关的肺纤维化，通常是致命的。从诊断开始，平均生存期为2-4年。血管生成，即生长新血管的能力，被认为是UIP典型纤维化反应所需的关键成分。四硫钼酸盐（TM）是一种用于治疗威尔逊病（一种影响肝脏的铜紊乱）的抗铜药物。TM还通过降低全身铜水平，对患有癌症的非威尔逊氏病患者和动物肿瘤模型产生抗血管生成作用。TM在UIP中试验的基本原理源于它在博来霉素肺纤维化小鼠模型中的成功应用，以及它的抗纤维化、抗炎、抗血管生成特性。这项针对既往治疗失败的UIP患者的开放标签研究将以三个月为间隔对患者进行为期一年的随访。在每次访问时，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射线）和6分钟步行测试。TM将被口服，剂量将被滴定以抑制血管生成，而不会引起铜缺乏的毒性。患者最初将每周监测一次，然后根据情况每两周监测一次或每月监测一次。主要终点是治疗12个月后肺功能的改变。研究记录将保存在一个密码保护的数据库中，只有研究人员可以访问。书面文件将保存在上锁的研究办公室的患者活页夹中。患者将给予参与本研究的书面知情同意。

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.