Effect of Bronchitol on Mucociliary Clearance in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR)-Modulator Treated Patients With Cystic Fibrosis With Moderate to Severe Lung Disease
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Average Rate of Mucociliary Clearance (MCC) Over 60 Minutes
研究概览
简要总结
This study will provide important mechanistic information regarding the effect of inhaled mannitol (Bronchitol) in people with cystic fibrosis (PwCF) with moderate to severe disease who are already using elexacaftor/tezacaftor/ivacaftor (E/T/I). Many patients have already discontinued hypertonic saline and other pulmonary therapies because of the profound effect of E/T/I of their symptoms and lung function. Further, because both inhaled osmotic agents (i.e., Bronchitol, hypertonic saline [HS]) and E/T/I are believed to exert their beneficial effects through improvements in mucociliary clearance (MCC), it is unknown if the combination of these therapies might be additive or are redundant in a population with moderate to severe disease where bronchiectasis and chronic infection persists, and where eventual decline in lung function is expected over time. This study, therefore, will be the first to determine whether "add on" therapy with inhaled mannitol is able to further accelerate MCC in E/T/I patients. These data would provide some guidance regarding the use of these approved therapies in PwCF.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able to provide informed consent
- •Age ≥ 18 at the time of screening
- •Diagnosis of cystic fibrosis (CF)
- •Regularly using elexacaftor/tezacaftor/ivacaftor (E/T/I) for ≥ 90 days
- •Forced Expiratory Volume in one second (FEV1) between 30% and 70%, inclusive, at time of screening
- •Denies active smoking or vaping
- •Clinically stable with no significant changes in health status within the 28 days prior to and including the screening visit
- •Patients on cycled inhaled antibiotics will need to be either on or off their antibiotic for 7 days prior to Visit 1 and not scheduled to cycle during the 2-week treatment period until after Visit 2
- •Has no other conditions that, in the opinion of the Site Investigator/Designee, would preclude informed consent, make study participation unsafe, complicate interpretation of study outcome data, or otherwise interfere with achieving the study objectives
排除标准
- •Use of an investigational drug within 28 days prior to and including the screening visit
- •Unable or unwilling to withhold hypertonic saline (HS) for 4 weeks (2 weeks prior to Visit 1 and 2 weeks between Visit 1 and Visit 2)
- •Unable or willing to withhold dornase alfa and bronchodilators on the morning of Visit 1 and Visit 2, until completion of study procedures
- •Initiation of new chronic CF pulmonary therapy (e.g. dornase alfa, azithromycin, inhaled antibiotic) within 28 days prior to and including the screening visit
- •No acute use of antibiotics (oral, inhaled, or intravenous) or acute use of systemic corticosteroids for respiratory tract symptoms within 28 days prior to and including the screening visit.
- •No chronic use of oral corticosteroids > 10 mg of prednisone or equivalent daily
- •Unable to tolerate albuterol or other bronchodilator
- •History of intolerance to HS or inhaled mannitol
- •Pregnancy or breast feeding
- •Have had more than 2 chest computed tomography (CT) in the past year or a combination of procedures that are believed to have exposed the subject's lungs to >150 millisievert (mSv)
- •History of significant hemoptysis (>60 mL) in the last three months
研究组 & 干预措施
Inhaled Mannitol
All study participants will receive the same study treatment. Study treatment will be dry powder mannitol 400 mg twice a day by oral inhalation (the contents of 10 capsules administered individually) for 14 days +/- 2 days.
干预措施: Mannitol Inhalant Product (Drug)
结局指标
主要结局
Average Rate of Mucociliary Clearance (MCC) Over 60 Minutes
时间窗: Day 14 (+/-2 days)
A whole lung region of interest (ROI) bordering the right lung is used to estimate (by computer analysis) whole lung retention of inhaled radiolabeled particles. Labeled particle counts are measured over a 60-minute period to determine the fraction of initial particle counts remaining. From this data, the investigators will determine the percentage of labeled particles cleared from the lung during the 60-minute observation period. The primary outcome will be expressed as a percent, representing total average rate of mucociliary clearance (MCC) in the whole right lung compartment over 60 minutes (MCC60).
次要结局
- Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Questionnaire Revised (CFQR-R)(Day 14(+/-2 days))
- Cough Clearance(Day 14 (+/-2 days))
- Rate of Mucociliary Clearance (MCC) Over 90 Minutes(Day 14(+/-2 days))
- Forced Expiratory Volume in One Second (FEV1) Percent of Predicted(Day 14 (+/-2 days))
- Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)(Day 14(+/-2 days))
- Respiratory Symptoms as Measured by the Treatment Satisfaction Questionnaire Measure (TSQM)(Day 14(+/-2 days))