Nicotine Treatment for Pulmonary Sarcoidosis: A Clinical Trial Pilot Study

描述（由申请人提供）：结节病是一种常见的不明原因的间质性肺病，目前的治疗通常无效和/或无法获得。该项目的最终目标是为结节病患者提供一种耐受性良好并立即可用的现有疗法的安全替代方案。在这方面，长期暴露于含尼古丁（烟草）产品一直被证明可以降低发生结节病的风险，最近的研究，包括我们的试点临床试验，表明尼古丁具有潜在的免疫调节作用，可能会改变肺结节病的病程。我们假设尼古丁治疗对肺结节病有效。本文拟定的临床试验初探性研究将提供计划后续确定性多机构试验所需的数据，以评估临床疗效。即，目标1将评估尼古丁治疗后用力肺活量（FVC）的变化。目标2将使用客观的放射学标准确定尼古丁治疗与单独的常规治疗相比是否减轻了肺部疾病的负担。这一目标将采用一种新的计算机化肺部CT图像分析工具，该工具被证明可以灵敏地检测肺结节病的各种表现。目标3将考虑未来II期和III期研究的替代临床终点，包括改善疲劳和疾病特异性症状。目的4将评估缓释透皮尼古丁在肺结节病人群中的安全性和耐受性。在这方面，尼古丁在阻塞性肺病患者中具有广泛的安全性记录（例如，吸烟相关），并且在我们先前的初步研究中耐受良好。然而，研究受试者的依从性和安全性将是未来临床疗效研究设计的重要决定因素。参与研究的中心（俄亥俄州州立大学和克利夫兰临床基金会）拥有大量结节病患者人群和丰富的结节病临床试验经验，完全有资格完成本研究。

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.