Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy and safety of chronic treatment with inhaled dry powder mannitol in subjects with cystic fibrosis. Previous studies have demonstrated an improvement in lung function related to small airways obstruction and a significant improvement in respiratory symptoms and quality of life after a 2 week treatment with mannitol. This current study seeks to support these early findings and to extend the evidence to support its use as a mucoactive therapy in cystic fibrosis. In particular, the hypothesis that enhanced mucus clearance will improve the lung function and clinical presentation in this population, will be investigated. We also hypothesize that enhanced mucociliary clearance will result in a sustained reduction in mucus load, thus providing less opportunity for bacteria to proliferate, affording a reduction in antibiotic use and hospitalizations. The initial 6 month blinded phase will be followed with an additional 6 months of open label treatment.

Official Title
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Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study

Conditions
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Cystic Fibrosis

Intervention / Treatment
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* Drug: Mannitol
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Main Inclusion Criteria: Written informed consent Confirmed diagnosis of cystic fibrosis Aged > 6 years FEV1 >30 % and < 90% predicted Able to perform all the techniques necessary to measure lung function Main Exclusion Criteria: Terminally ill or listed for lung transplantation Had a lung transplant Using nebulised hypertonic saline Significant episode of haemoptysis (>60 mL) in the three months prior to enrolment Recent myocardial infarction or cerebral vascular accident Breast feeding or pregnant, or plan to become pregnant while in the study participating in another investigative drug study, parallel to, or within 4 weeks of study entry Allergy or intolerance to mannitol Using beta blockers Have a condition or be in a situation which in the Investigator's opinion may put the subject at significant risk, may confound results or may interfere significantly with the patient's participation in the study

Ages Eligible for Study
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Minimum Age: 6 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Mannitol<br>* 400mg BD for 6 months followed by a 6 month open label period<br>|
| Placebo Comparator: 2<br> | Drug: placebo<br>* placebo BD for 6 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF compared to control |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effects of 400 mg twice-daily administration of IDPM on FEV1 in patients with CF on existing RhDNase treatment compared to control. (key objective) |  | 6 months | 
| Reduces pulmonary exacerbations in those taking RhDNase as a sub-group and in the total cohort (key objective) |  | 6 months / 12 months | 
| Improves quality of life (key objective) |  | 6 months | 
| Reduces days on IV antibiotics, rescue oral or inhaled antibiotics |  | 6 months / 12 months | 
| Reduces days in hospital due to pulmonary exacerbations |  | 6 months / 12 months | 
| Improves other measures of lung function |  | 6 months | 
| Demonstrates an appropriate safety profile (adverse events, haematology, biochemistry, change in bronchodilator response, sputum microbiology, physical examination) |  | 6 months / 12 months | 
| Reduces hospital and community care costs |  | 6 months / 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mannitol, Cystic Fibrosis, Mucolytic, Exacerbation, FEV1, Quality of Life