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

I/II 期试验四硫代钼酸盐 (TM) 在患有普通间质性肺炎的 PTS 中的应用

• 批准号: 7603721
• 负责人: KEVIN R FLAHERTY
• 金额: $ 0.05万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-03-01 至 2007-09-16
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7603721
• 关键词: Affect; Angiogenesis Inhibitors; Animals; Anti-Inflammatory Agents; Blood Vessels; Cicatrix; Computer Retrieval of Information on Scientific Projects Database; Copper; Databases; Diagnosis; Disease; Dose; End Point; Funding; Grant; Hamman-Rich syndrome; Hepatolenticular Degeneration; Informed Consent; Institution; Label; Liver; Lung; Malignant Neoplasms; Modeling; Monitor; Patients; Pharmaceutical Preparations; Phase; Property; Pulmonary Fibrosis; Quality of life; Questionnaires; Records; Research; Research Personnel; Resolution; Resources; Source; Testing; Time; Toxic effect; United States National Institutes of Health; Visit; Walking; Writing; X-Ray Computed Tomography; angiogenesis; hypocupremia; indium-bleomycin; mouse model; pulmonary function; response; stem; tetrathiomolybdate; tumor

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.'

这个子项目是许多利用 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。 肺间质性肺炎（UIP）是一种与肺瘢痕形成相关的肺纤维化，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典型的纤维化反应所需的关键组成部分。 四硫代钼酸盐（TM）是一种抗铜药物，用于治疗威尔逊病（一种影响肝脏的铜紊乱）。 TM还通过降低全身铜水平，在患有癌症的非威尔逊病患者和动物肿瘤模型中产生抗血管生成作用。 在UIP中进行TM试验的基本原理源于其在肺纤维化的博来霉素小鼠模型中的成功使用，以及其抗纤维化、抗血管生成的特性。 这项针对既往治疗失败的UIP患者的开放标签研究将以3个月的间隔对患者进行为期一年的随访。 在每次访视时，将进行肺功能研究和生活质量问卷调查。 将在基线和治疗12个月后进行高分辨率CT扫描（一种X射线）和6分钟步行试验。 TM将口服给药，并滴定剂量以抑制血管生成，而不会引起铜缺乏毒性。 最初每周监测一次患者，然后每两周和每月（如适用）监测一次。 主要终点是治疗12个月后肺功能的变化。 研究记录将保存在密码保护的数据库中，仅研究者可访问。 书面文件将保存在上锁的研究办公室的患者文件夹中。 患者将提供参与本研究的书面知情同意书。'