CLINICAL TRIAL: DENUFOSOL TETRASODIUM INHALATION SOLUTION IN PATIENTS WITH MILD

临床试验：地纽福索四钠吸入溶液用于轻度患者

• 批准号: 7718527
• 负责人: Theodore Geh-Lu Liou
• 金额: $ 0.09万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-03-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718527
• 关键词: Abnormal ion transport; Agonist; Breathing; Bronchiectasis; Bypass; Chloride Channels; Chloride Ion; Chronic; Class; Clinical Trials; Computer Retrieval of Information on Scientific Projects Database; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Daily; Development; Disease; Dose; Epithelial; Frequencies; Functional disorder; Funding; Gastrointestinal Diseases; Generations; Genes; Goblet Cells; Grant; Hereditary Disease; INS37217; Inflammation; Institution; Liquid substance; Lung; Mucins; Mucociliary Clearance; Mutation; Nebulizer; P2Y2 receptor; Patients; Placebos; Process; Pulmonary Cystic Fibrosis; Research; Research Personnel; Resources; Respiratory Tract Infections; Respiratory physiology; Safety; Sodium; Solutions; Source; Time; United States National Institutes of Health; Valsava sinus; Week; absorption; airway epithelium; airway surface liquid; apical membrane; base; denufosol tetrasodium; insight; novel; novel strategies; protein function; reproductive

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. Cystic fibrosis (CF) is a recessive genetic disease, characterized by pulmonary and sinus disease, and gastrointestinal and reproductive tract dysfunction. The disease is caused by mutations in the cystic fibrosis transmembrane regulator (CFTR) gene, which encodes for an apical membrane epithelial protein that functions as a c-AMP-regulated chloride channel and a regulator of other channels (Boucher, 1994). Defective CFTR results in abnormal ion transport and depleted airway surface liquid volume with reduced mucociliary clearance and a propensity for chronic infection of the respiratory tract with resulting inflammation, progressive airway damage and bronchiectasis. New therapies are being developed for the treatment of CF, based on insights into the pathophysiology of the disease. P2Y2 receptor agonists represent a novel approach to the treatment of CF that attempts to bypass defective CFTR in airway epithelia and, instead, take advantage of the integrated actions of this class of agents on mucociliary clearance that are not dependent on CFTR. These agents act by stimulating the P2Y2 receptor, which results in chloride ion (Cl-) and liquid secretion and the inhibition of sodium (Na+) absorption to hydrate the airway surface liquid layer and create a more normal periciliary fluid milieu,while also stimulating mucin secretion from goblet cells and increasing ciliary beat frequency. Denufosol tetrasodium (INS37217) inhalation solution (denufosol) is a novel second generation, chemically stable, selective P2Y2 receptor agonist under development by InspirePharmaceuticals, Inc. Denufosol may have the ability to restore or maintain mucociliary clearance in patients relatively early in the CF lung disease process, which may preserve lung function and lessen the inevitable repeat cycles of pulmonary bacterial colonization, pulmonary exacerbations, and chronic lung function decline. The objective of this study is evaluate the efficacy, safety and tolerability of a 60 mg nebulizer dose of denufosol compared to placebo when administered three times daily over 24 weeks in patients with mild CF lung disease.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 囊性纤维化（CF）是一种隐性遗传病，以肺部和鼻窦疾病以及胃肠道和生殖道功能障碍为特征。该疾病是由囊性纤维化跨膜调节器 (CFTR) 基因突变引起，该基因编码顶膜上皮蛋白，充当 c-AMP 调节的氯离子通道和其他通道的调节器 (Boucher，1994)。 CFTR 缺陷会导致离子传输异常、气道表面液量减少、粘膜纤毛清除率降低以及呼吸道慢性感染倾向，从而导致炎症、进行性气道损伤和支气管扩张。 基于对该疾病病理生理学的深入了解，正在开发治疗 CF 的新疗法。 P2Y2 受体激动剂代表了一种治疗 CF 的新方法，试图绕过气道上皮细胞中缺陷的 CFTR，而是利用此类药物对不依赖于 CFTR 的粘膜纤毛清除的综合作用。这些药物通过刺激 P2Y2 受体发挥作用，导致氯离子 (Cl-) 和液体分泌并抑制钠 (Na+) 吸收，从而水合气道表面液体层并创造更正常的纤毛周围液体环境，同时还刺激杯状细胞的粘蛋白分泌并增加纤毛跳动频率。地纽福索四钠 (INS37217) 吸入溶液 (地纽福索) 是 InspirePharmaceuticals, Inc. 正在开发的新型第二代化学稳定的选择性 P2Y2 受体激动剂。地纽福索可能能够在 CF 肺部疾病过程的相对早期恢复或维持患者的粘液纤毛清除能力，这可能会保护肺功能并减少不可避免的重复周期 肺部细菌定植、肺部病情加重和慢性肺功能下降。 本研究的目的是评估 60 mg 雾化器剂量的地纽福索与安慰剂相比，在 24 周内每天给药 3 次，对轻度 CF 肺病患者的疗效、安全性和耐受性。