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

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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.