Hypertonic Saline for Cystic Fibrosis

高渗盐水治疗囊性纤维化

• 批准号: 8523987
• 负责人: David Busick
• 金额: $ 150.94万
• 依托单位: PARION SCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8523987
• 关键词: Acute; Adhesions; Aerosols; Affect; Bicarbonates; Breathing; Buffers; Cannulas; Caring; Chronic; Clinical; Clinical Research; Clinical Trials; Cystic Fibrosis; Data; Dehydration; Deposition; Development; Device Designs; Devices; Disease; Dose; Drug Formulations; Ensure; Excision; Frequencies; Future; Genetic Crossing Over; Goals; Hereditary Disease; Hour; Human; Hydration status; Individual; Infection; Infectious Agent; Label; Lubricants; Lung; Lung diseases; Measures; Mucociliary Clearance; Mucous body substance; Nebulizer; Nose; Oropharyngeal; Patients; Pattern; Performance; Peripheral; Pharmaceutical Preparations; Pharmacodynamics; Phase; Physical therapy; Placebos; Preparation; Program Development; Property; Publishing; Pulmonary Cystic Fibrosis; Quality of life; Rehydrations; Respiratory physiology; Safety; Saline; Science; Sleep; Small Business Innovation Research Grant; Sodium Bicarbonate; Sputum; Surface; Testing; Therapeutic; Therapeutic Effect; Time; Treatment Protocols; Water; adverse outcome; airway inflammation; airway surface liquid; base; compliance behavior; cystic fibrosis airway; cystic fibrosis patients; design; effective therapy; ergonomics; human subject; improved; meetings; mortality; novel; open label; public health relevance; pulmonary function; response; safety testing; standard of care; success; therapy development

DESCRIPTION (provided by applicant): Cystic fibrosis (CF) is an autosomal lethal disease characterized that affects ~30,000 individuals in the US. CF lung disease, the major cause of mortality in CF, is caused by dehydration of airway secretions that leads to mucous adhesion, infection and airways inflammation. A simple means to restore hydration and mucous clearance in CF airways is the inhalation of hypertonic saline (HS), which osmotically draws water onto the airway surface. Rehydration of the lubricant layer of the airway surface liquid facilitates mucociliary clearance (MCC) and therefore the removal of inhaled infectious agents. Previously published evidence has shown that short-term administration of HS improves the rheologic properties and transportability of sputum, hydrates the airway surface, and improves MCC and lung function in patients with CF. Recent clinical studies support the efficacy of daily HS treatments for CF demonstrating improvements in lung function, a reduction in pulmonary exacerbations, and improvements in quality of life. As a result, inhaled HS is becoming a standard of care for CF and is now used by ~50% of patients nationwide. One consequence of the addition of HS to CF treatment regimens is the time required by CF patients for its administration. Daily HS treatments require ~1 hour of time commitment, which is superimposed on the ~2 hours of care typically asked of these patients for other aerosols and physiotherapy. Thus, there is a great need to reduce the treatment burden (time commitment) of this therapy to improve the quality of life of CF patients. Parion Science's goal is to develop therapies that provide major improvements in efficacy over current treatments for CF. Parion is developing a specialized device of overnight administration of HS that will reduce daytime treatment requirements for CF patients. Parion has developed a novel nasal aerosol delivery device designed to administer a therapeutic dose of HS overnight that is comfortable, quiet, and compatible with sleep. The device was tested in a clinical deposition study where it achieved a higher than expected pulmonary deposition of HS aerosol, confirming that the device will be able to achieve a sufficiently high deposited pulmonary dose of HS to support future clinical trials. Based on the success of the deposition study, Parion will continue the development program by evaluating the tolerability and efficacy of HS delivery via the device in a Phase 2 clinical study. If successful, we believe that this approach will improve the quality of life of CF patients by decreasing the treatment burden associated with daily HS treatments and improve compliance of this therapy.

描述（由申请方提供）：囊性纤维化（CF）是一种常染色体致死性疾病，在美国影响约30，000例患者。CF肺部疾病是CF死亡的主要原因，是由气道分泌物脱水导致粘膜粘附、感染和气道炎症引起的。恢复CF气道中的水合作用和粘液清除的简单方法是吸入高渗盐水（HS），其将水吸引到气道表面上。气道表面液体的润滑层的再水化促进粘膜纤毛清除（MCC），并因此促进吸入的感染剂的去除。 先前发表的证据表明，短期给予HS可改善CF患者痰液的流变学特性和可转运性，使气道表面水合，并改善MCC和肺功能。最近的临床研究支持每日HS治疗CF的疗效，证明了肺功能的改善、肺部急性加重的减少和生活质量的改善。因此，吸入HS正在成为CF的标准治疗，目前全国约50%的患者使用。CF治疗方案中添加HS的一个后果是CF患者对其给药所需的时间。每日HS治疗需要约1小时的时间承诺，这是叠加在约2小时的护理通常要求这些患者的其他气雾剂和物理治疗。因此，非常需要减少这种疗法的治疗负担（时间承诺），以改善CF患者的生活质量。 Parion Science的目标是开发治疗方法，与目前的CF治疗方法相比，其疗效有重大改善。Parion正在开发一种专门的夜间HS给药装置，这将减少CF患者的日间治疗需求。Parion开发了一种新型鼻气雾剂输送装置，设计用于在夜间给予治疗剂量的HS，该装置舒适、安静且与睡眠相容。在临床沉积研究中对该器械进行了测试，其中HS气雾剂的肺部沉积高于预期，证实该器械能够实现足够高的HS肺部沉积剂量，以支持未来的临床试验。基于沉积研究的成功，Parion将通过在II期临床研究中评价通过器械输送HS的耐受性和有效性来继续开发项目。如果成功，我们相信这种方法将提高CF的生活质量 通过减少与每日HS治疗相关的治疗负担并提高该治疗的依从性来治疗患者。