Nicotine Treatment for Pulmonary Sarcoidosis: A Clinical Trial Pilot Study

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DESCRIPTION (provided by applicant): Sarcoidosis is a common interstitial lung disease of unknown cause for which current therapies are often ineffective and/or inaccessible. The ultimate goal of this project is to deliver a safe alternative to current therapies that will be wel-tolerated and immediately available to sarcoidosis patients. In this regard, chronic exposure to nicotine-containing (tobacco) products is consistently shown to reduce the risk of developing sarcoidosis, and recent studies, including our pilot clinical trial, indicate that nicotine has potnt immune modulating effects that could alter the course of pulmonary sarcoidosis. We hypothesize that nicotine treatment will be efficacious for the treatment of pulmonary sarcoidosis. The Clinical Trial Pilot Study proposed herein will provide data required for the planning of subsequent, definitive multi-institutional trials to assess clinical efficacy. Namely, Aim 1 will assess changes in forced vital capacity (FVC) in response to nicotine treatment. Aim 2 will determine if nicotine treatment reduces the burden of lung disease, using objective radiographic criteria, compared to conventional therapies alone. This aim will employ a novel computerized lung CT image analysis tool that is demonstrated to sensitively detect various manifestations of pulmonary sarcoidosis. Aim 3 will consider alternative clinical endpoints for a future Phase II and III studies, including improvements in fatigue and disease-specific symptoms. Aim 4 will assess the safety and tolerability of sustained-release transdermal nicotine in the pulmonary sarcoidosis population. In this regard, nicotine has an extensive track record of safety in patients with obstructive lung disease (e.g., smoking-related), and was well tolerated in our previous pilot study. However, study subject compliance and safety will be important determinants used for the design of future clinical efficacy studies. The participating centers, Ohio State University and Cleveland Clinic Foundation, have large sarcoidosis patient populations and extensive experience with sarcoidosis clinical trials, and are well-qualified to complete this study.