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病因不明的间质性肺疾病，目前的治疗方法往往无效和/或难以获得。该项目的最终目标是提供一种安全的替代现有治疗方法，这种方法耐受性良好，可立即用于结节病患者。在这方面，长期接触含尼古丁（烟草）产品一直被证明可以降低患结节病的风险，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，可以改变肺结节病的病程。我们假设尼古丁治疗对肺结节病是有效的。本文提出的临床试验先导研究将为规划后续确定的多机构试验以评估临床疗效提供所需的数据。也就是说，Aim 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，与常规治疗相比，确定尼古丁治疗是否减轻了肺部疾病的负担。本目的将采用一种新的计算机肺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。目的3将考虑未来II期和III期研究的替代临床终点，包括疲劳和疾病特异性症状的改善。目的4将评估肺结节病人群中透皮尼古丁缓释的安全性和耐受性。在这方面，尼古丁在阻塞性肺疾病（例如吸烟相关）患者中具有广泛的安全性记录，并且在我们之前的试点研究中耐受性良好。然而，研究对象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，俄亥俄州立大学和克利夫兰诊所基金会，有大量的结节病患者群体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.