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| Name | Class |
|---|---|
| Chiesi USA, Inc. | INDUSTRY |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Mannitol Inhalant Product | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Day 14 (+/-2 days) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 14 (+/-2 days) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Subhashini A Sellers, MD, MSCR | University of North Carolina, Chapel Hill | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | 27599 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Posted | Mean | Standard Deviation | percent cleared over 60 minutes | Day 14 (+/-2 days) |
|
From the time of signing informed consent through Visit 2 completion, up to 4 weeks.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Inhaled mannitol intolerance as demonstrated by FEV1 decline | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Subhashini Sellers, MD, MSCR | University of North Carolina at Chapel Hill | 919-966-2531 | sasellers@med.unc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 14, 2024 | Oct 21, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003550 | Cystic Fibrosis |
| ID | Term |
|---|---|
| D010182 | Pancreatic Diseases |
| D004066 | Digestive System Diseases |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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| ID | Term |
|---|---|
| D008353 | Mannitol |
| ID | Term |
|---|---|
| D013402 | Sugar Alcohols |
| D000438 | Alcohols |
| D009930 | Organic Chemicals |
| D002241 | Carbohydrates |
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|
| 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). |
| 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. | 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. | 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. | 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. | Day 14(+/-2 days) |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Baseline Forced Expiratory Volume in 1 Second (FEV1) | Mean | Standard Deviation | percent predicted |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | percent cleared over 30 minutes | Day 14 (+/-2 days) |
|
|
|
|
| Secondary | 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). | Posted | Mean | Standard Deviation | percent cleared over 90 minutes | Day 14(+/-2 days) |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | percent predicted | Day 14 (+/-2 days) |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Day 14(+/-2 days) |
|
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Day 14(+/-2 days) |
|
|
|
|
| Secondary | 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. | 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. | Posted | Day 14(+/-2 days) |
|
|
| 0 |
| 13 |
| 0 |
| 13 |
| 3 |
| 13 |
| Lightheadedness | Nervous system disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D030342 |
| Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D007232 | Infant, Newborn, Diseases |