Novel Therapies in Idiopathic Pulmonary Fibrosis

特发性肺纤维化的新疗法

• 批准号: 7227046
• 负责人: Kevin K Brown
• 金额: $ 17.97万
• 依托单位: NATIONAL JEWISH HEALTH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-05-01 至 2010-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7227046
• 关键词: Acetylcysteine; Activities of Daily Living; Biological Assay; Biological Markers; Biological Monitoring; Breathing; Bronchoalveolar Lavage Fluid; Cessation of life; Chronic; Clarithromycin; Clinic Visits; Clinical Research; Data; Deterioration; Disease; Disease Progression; Disorder by Site; Dyspnea; End Point; Epithelial; Epoprostenol; Extracellular Matrix; Fibroblasts; Fibrosis; Goals; Hamman-Rich syndrome; Hospitalization; Inflammation; Institution; Investigation; Liquid substance; Lung; Malignant neoplasm of lung; Mind; Myofibroblast; Oxidants; Patients; Pharmaceutical Preparations; Pravastatin; Prostaglandins; Prostaglandins I; Quality of life; Rate; Relative (related person); Respiratory physiology; Severities; Time; Transforming Growth Factor beta; Work; abstracting; alveolar epithelium; analog; angiogenesis; clinical effect; functional status; improved; interstitial; mortality; novel; prevent

DESCRIPTION (provided by applicant): The survival of patients with idiopathic pulmonary fibrosis (IPF) is short, their quality of life is poor, and spontaneous progression of their disease is almost universal. We propose to collaborate with like-minded institutions to increase the pace of investigation into treatment options with a goal of prolonging survival, improving quality of life, and increasing functional capacity in these patients. The overall objective in this proposal is to evaluate, in a multicentered clinical research network, the efficacy of one multi-drug (N-acetyl cysteine [NAC], clarithromycin, and pravastatin) and a novel therapy (prostaglandin 12 [PG12], prostacyclin or its analogues) in the treatment of IPF. Our primary endpoint will be to determine if one or both of these approaches delays the time to death or decline in FVC. Our secondary endpoints will be to determine if these approaches improve quality of life, increase functional status, or delay loss of lung function. Exploratory endpoints will be to determine in these therapies decrease in unplanned clinic visits or hospitalizations and favorably alter proposed biologic markers of disease activity. Our hypothesis is that NAC, clarithromycin, and paravastatin will have favorable biologic and clinical effects on three sites of disease activity, abnormal alveolar epithelium, lymphoplasmacytic inflammation, and persistence of interstitial myofibroblasts. We hypothesize that PG12 will block the differentiation of fibroblasts into myofibroblasts thereby delaying or preventing the progression of fibrosis. A secondary objective will be to determine if the ability of bronchoalveolar lavage fluid to convert fibroblasts to myofibroblasts can be used as a bioassay to monitor biologic disease activity. Our hypothesis is that active TGF-beta in BAL fluid is responsible for this activity and can be favorably altered by PG12 therapy. (End of Abstract)

描述（由申请人提供）： 特发性肺纤维化（IPF）患者的存活率很短，生活质量差，并且疾病的自发进展几乎是普遍的。 我们建议与志趣相投的机构合作，以提高对治疗方案的调查步伐，目的是延长生存，改善生活质量并提高这些患者的功能能力。 该提案的总体目的是在多中心临床研究网络中评估一种多药（N-乙酰基半胱氨酸[NAC]，Clarithromycin和pravastatin）的功效以及一种新颖的疗法（Prostaglandin 12 [pg12]，Prostacyclin或Prostacyclin或Prostacyclin或其类似物）。 我们的主要终点是确定其中一种或两种方法是否延迟了FVC死亡或下降的时间。 我们的次要终点是确定这些方法是否改善了生活质量，提高功能状态或延迟肺功能损失。 探索性终点是在这些疗法中确定计划外的诊所就诊或住院治疗，并有利地改变了疾病活动的生物学标志物。 我们的假设是，NAC，Clarithromycin和paravastatin将对疾病活性的三个部位，异常肺泡上皮，淋巴细胞囊肿性炎症以及间质肌纤维细胞的持久性具有有利的生物学和临床作用。 我们假设PG12将阻止成纤维细胞的分化为肌纤维细胞，从而延迟或防止纤维化的进展。 次要目标是确定支气管肺泡灌洗液将成纤维细胞转换为肌纤维细胞的能力是否可以用作监测生物学疾病活动的生物测定方法。 我们的假设是，BAL流体中的主动TGF-beta是为此活性负责的，并且可以通过PG12治疗来改变。 （抽象的结尾）