Trial Outcomes & Findings for Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis (NCT NCT05740618)

Last Updated: 2026-01-07

Results Overview

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).

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

14 participants

Primary outcome timeframe

Day 14 (+/-2 days)

Results posted on

2026-01-07

Participant Flow

Participant milestones

Participant milestones
Measure	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. 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.
Overall Study STARTED	14
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	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. 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.
Overall Study Did not meet Inclusion/Exclusion criteria	1
Overall Study Physician Decision	1

Baseline Characteristics

Inhaled Mannitol on Mucociliary Clearance in Moderate to Severe Cystic Fibrosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Age, Continuous	38.0 years STANDARD_DEVIATION 10.3 • n=37 Participants
Sex: Female, Male Female	6 Participants n=37 Participants
Sex: Female, Male Male	6 Participants n=37 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=37 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=37 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=37 Participants
Race (NIH/OMB) Asian	0 Participants n=37 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=37 Participants
Race (NIH/OMB) Black or African American	0 Participants n=37 Participants
Race (NIH/OMB) White	12 Participants n=37 Participants
Race (NIH/OMB) More than one race	0 Participants n=37 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=37 Participants
Region of Enrollment United States	12 Participants n=37 Participants
Baseline Forced Expiratory Volume in 1 Second (FEV1)	48.6 percent predicted STANDARD_DEVIATION 10.3 • n=37 Participants

PRIMARY outcome

Timeframe: Day 14 (+/-2 days)

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Average Rate of Mucociliary Clearance (MCC) Over 60 Minutes	14.8 percent cleared over 60 minutes Standard Deviation 6.5

SECONDARY outcome

Timeframe: Day 14 (+/-2 days)

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.

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Cough Clearance	0.30 percent cleared over 30 minutes Standard Deviation 0.06

SECONDARY outcome

Timeframe: 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 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).

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Rate of Mucociliary Clearance (MCC) Over 90 Minutes	18.2 percent cleared over 90 minutes Standard Deviation 7.7

SECONDARY outcome

Timeframe: Day 14 (+/-2 days)

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.

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Forced Expiratory Volume in One Second (FEV1) Percent of Predicted	46.9 percent predicted Standard Deviation 11.3

SECONDARY outcome

Timeframe: Day 14(+/-2 days)

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.

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Questionnaire Revised (CFQR-R)	78.3 score on a scale Standard Deviation 13.7

SECONDARY outcome

Timeframe: Day 14(+/-2 days)

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.

Outcome measures

Outcome measures
Measure	Inhaled Mannitol n=12 Participants 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. 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.
Respiratory Symptoms as Measured by the Cystic Fibrosis Respiratory Symptom Diary and Chronic Respiratory Infection Symptom Score (CFRSD-CRISS)	33.3 score on a scale Standard Deviation 7.2

SECONDARY outcome

Timeframe: Day 14(+/-2 days)

Population: While participants completed the questionnaire, we are unable to generate a reportable result. As we learned late in the process, the scoring manual required to code responses and calculate results is proprietary, and the rights for its use were not secured. This data will never be analyzed in the future. The study protocol was not amended to reflect this change.

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.

Outcome measures

Outcome data not reported

Adverse Events

Inhaled Mannitol

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Inhaled Mannitol n=13 participants at risk 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. 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.
Respiratory, thoracic and mediastinal disorders Inhaled mannitol intolerance as demonstrated by FEV1 decline	7.7% 1/13 • Number of events 1 • From the time of signing informed consent through Visit 2 completion, up to 4 weeks.
Nervous system disorders Lightheadedness	7.7% 1/13 • Number of events 1 • From the time of signing informed consent through Visit 2 completion, up to 4 weeks.
Respiratory, thoracic and mediastinal disorders Cough	7.7% 1/13 • Number of events 1 • From the time of signing informed consent through Visit 2 completion, up to 4 weeks.

Additional Information

Subhashini Sellers, MD, MSCR

University of North Carolina at Chapel Hill

Phone: 919-966-2531

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place