Clinical trial NCT05740618: Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis
Official title: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Cystic Fibrosis
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Chiesi USA, Inc.
First posted: 2023-02-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* 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
* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Average change in rate of mucociliary clearance (MCC) over 60 minutes from Visit 1 (pre-mannitol) to Visit 2 (post-mannitol)
timeFrame: Day 1 to Day 14(+/-2 days)
Secondary outcomes:
measure: Average change in cough clearance from Visit 1 (pre-mannitol) to Visit 2 (post-mannitol)
timeFrame: Day 1 to Day 14(+/-2 days)
measure: Average change in rate of mucociliary clearance (MCC) over 90 minutes from Visit 1 (pre-mannitol) to Visit 2 (post-mannitol)
timeFrame: Day 1 to Day 14(+/-2 days)
measure: Change in forced expiratory volume in one second (FEV1) % of predicted from Visit 1 to Visit 2
timeFrame: Day 1 to Day 14(+/-2 days)
measure: Change in respiratory symptoms as measured by the Cystic Fibrosis Respiratory Questionnaire Revised (CFQR-R) from Visit 1 to Visit 2
timeFrame: Day 1 to Day 14(+/-2 days)
measure: Change in respiratory symptoms as measured by the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS) from Visit 1 to Visit 2
timeFrame: Day 1 to Day 14(+/-2 days)
measure: Change in respiratory symptoms as measured by the Treatment Satisfaction Questionnaire Measure (TSQM) from Visit 1 to Visit 2
timeFrame: Day 1 to Day 14(+/-2 days)
Other outcomes:
Locations:
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Subhashini A Sellers, MD, MSCR
role: PRINCIPAL_INVESTIGATOR
References: