Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis

NCT ID: NCT05740618

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 14 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-03-28
• Study Completion Date: 2025-01-29

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.

Conditions

Cystic Fibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Mannitol Inhalant Product

Intervention Type: DRUG

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.

Interventions

Mannitol Inhalant Product

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.

Intervention Type: DRUG

Other Intervention Names

Bronchitol; dry powder mannitol

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
• 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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chiesi USA, Inc.

INDUSTRY

Sponsor Role: collaborator

University of North Carolina, Chapel Hill

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Subhashini A Sellers, MD, MSCR

Role: PRINCIPAL_INVESTIGATOR

University of North Carolina, Chapel Hill

Locations

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

22-1790

Identifier Type: -

Identifier Source: org_study_id