Cystic FibrosisPhase 4NCT05740618
Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis
A Phase 4 study testing Mannitol Inhalant Product in people with Cystic Fibrosis, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Mannitol Inhalant Product
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Mar 2023to 29 Jan 2025
- Phase
- Phase 4
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina at Chapel Hill
Chapel Hill, North Carolina, 27599
About this study
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
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.
- Conditions
- Cystic Fibrosis
- Being tested
- Mannitol Inhalant Product
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mannitol Inhalant ProductDrug
Also called Bronchitol; dry powder mannitol
A sugar alcohol indicated as an add-on maintenance therapy to improve pulmonary function in adult patients 18 years of age and older with cystic fibrosis.
| Study group | Role | What they receive |
|---|---|---|
| Inhaled Mannitol | Experimental | 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. Receives: Drug: Mannitol Inhalant Product |
What is being measured
The primary outcome is the main question the study is designed to answer.
Average Rate of Mucociliary Clearance (MCC) Over 60 Minutes
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).
Measured: Day 14 (+/-2 days)
Secondary outcomes (6)
Cough Clearance
Subjects will cough a total of 30 times over a 30-minute period to assess cough clearance by gamma imaging over that period. Clearance will be determined by measuring the decrease in radiolabeled Tc99m-sulfur colloid in the lungs over time expressed as a percent cleared.
Measured: Day 14 (+/-2 days)
Rate of Mucociliary Clearance (MCC) Over 90 Minutes
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 90-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 90-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 90 minutes (MCC90).
Measured: Day 14(+/-2 days)
Forced Expiratory Volume in One Second (FEV1) Percent of Predicted
FEV1 is measured by spirometry. On each occasion, the best of 3 trials, based on American Thoracic Society (ATS)/European Respiratory Society (ERS) criteria. The best FEV1 (from trial with highest sum of FEV1 and Forced Vital Capacity (FVC)) will be recorded and reported as percent of predicted.
Measured: Day 14 (+/-2 days)
Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Questionnaire Revised (CFQR-R)
The CFQ-R (Cystic fibrosis Questionnaire - Revised) is a detailed, rigorously designed and validated self-report instrument designed to measure quality of life in patients with CF who are 14 years and older. This instrument was developed as the first CF-specific, health-related Quality of Life (QOL) measure. The respiratory domain has a 0-100 scale, with higher values signifying less severe symptoms.
Measured: Day 14(+/-2 days)
Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)
The CFRSD-CRISS is an 8-item, patient-centered, self-report outcome measure evaluating symptom severity over the prior 24 hours in 8 domains central to CF. Each question is assigned a score from 0-4 based on the response, with zero reflecting the absence of the symptom and four reflecting that the symptoms is present 'a great deal' or 'extremely'. A summed score (range from 0-24) is converted to a 0-100 scale, where lower scores indicate fewer symptoms.
Measured: Day 14(+/-2 days)
Respiratory Symptoms as Measured by the Treatment Satisfaction Questionnaire Measure (TSQM)
The TSQM is a 14-question standardize measure for assessment of self-reported treatment satisfaction and has been valued for use of inhaled medications in people with CF. The TSQM items are answered on 5- or 7-point Likert type scale and cover four domains, corresponding to distinct aspects related to the satisfaction of patients with their treatment (Effectiveness; Side effects; Convenience and Global satisfaction). The questionnaire is scored on a 0-100 scale, with higher values indicated greater satisfaction.
Measured: Day 14(+/-2 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Feb 2023
- Study start28 Mar 2023
- Primary completion29 Jan 2025
- Study completion29 Jan 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Chiesi USA, Inc.
- Responsible party
- Sponsor
- Investigators
- Subhashini A Sellers, MD, MSCR, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05740618
- Sponsor's protocol ID
- 22-1790
- Status last verified
- Oct 2025
- First submitted
- 3 Feb 2023
- Last updated
- 7 Jan 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No