Please select the eligibility criteria that correspond to the clinical trial below.
Title: Long Term Administration of Inhaled Dry Powder Mannitol In Cystic Fibrosis - A Safety and Efficacy Study
Brief Summary: 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.


Options:
A: Inclusion Criteria:

1. Have given written informed consent to participate in this study in accordance with local regulations
2. Have a confirmed diagnosis of cystic fibrosis (positive sweat chloride value ≥ 60 mEq/L) and/or genotype with two identifiable mutations consistent with CF, accompanied by one or more clinical features consistent with the CF phenotype)
3. Be aged \> 6 years old
4. Have FEV1 \>40 % and \< 90% predicted
5. Be able to perform all the techniques necessary to measure lung function

Exclusion Criteria:

1. Investigators, site personnel directly affiliated with this study, or their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biologically or legally adopted.
2. Be considered "terminally ill" or eligible for lung transplantation
3. Have had a lung transplant
4. Be using nebulized hypertonic saline in the 4 weeks prior to visit 1
5. Have had a significant episode of hemoptysis (\>60 mL) in the three months prior to enrolment
6. Have had a myocardial infarction in the three months prior to enrolment
7. Have had a cerebral vascular accident in the three months prior to enrolment
8. Have had major ocular surgery in the three months prior to enrolment
9. Have had major abdominal, chest or brain surgery in the three months prior to enrolment
10. Have a known cerebral, aortic or abdominal aneurysm
11. Be breast feeding or pregnant, or plan to become pregnant while in the study
12. Be using an unreliable form of contraception (female subjects at risk of pregnancy only)
13. Be participating in another investigative drug study, parallel to, or within 4 weeks of visit 0
14. Have a known allergy to mannitol
15. Be using beta blockers
16. Have uncontrolled hypertension - systolic BP \> 190 and / or diastolic BP \> 100
17. 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
18. Be 'Mannitol Tolerance Test positive'

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B: Inclusion Criteria:

1. Confirmed diagnosis of cystic fibrosis (sweat test/genotype)
2. Aged 8 years or older
3. Have FEV1 between 40% and 80% of predicted for height, age and gender OR a decrease in FEV1 of 20% or more than that recorded 6-12 months previously.
4. As determined by the investigator, are capable and willing to

   * Use the study diary as required for this protocol
   * Able to perform all of the techniques necessary to measure lung function
   * Able to administer the dry powder mannitol
5. Are capable of and have given informed consent
6. Clinically stable at study entry

Exclusion Criteria:

1. Investigators, site personnel directly affiliated with this study, and their immediate families.
2. Subjects under the age of 8 years.
3. Subjects with currently active asthma
4. Subjects using hypertonic saline treatment in the last 2 weeks
5. Considered "terminally ill" or listed for transplantation
6. Requiring home oxygen or assisted ventilation
7. Colonisation with Burkholderia cepacia
8. Significant episode of hemoptysis (\>60 mls) in the previous 12 months
9. Myocardial Infarction in the six months prior to enrolment.
10. Cerebral Vascular Accident in the six months prior to enrolment.
11. Ocular surgery in the three months prior to enrolment.
12. Abdominal surgery in the three months prior to enrolment.
13. Subjects who are breast feeding or pregnant.
14. Female subjects of reproductive capability, not using a reliable form of contraception
15. Inability to obtain informed consent from the subject or subject's authorised representative.
16. Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of study entry.
17. Known intolerance to mannitol or beta2 agonists.
18. Uncontrolled hypertension - systolic BP \> 160 and or diastoli
C: 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
D: Inclusion Criteria:

* Known diagnosis of cystic fibrosis (sweat test or genotype)
* Of either gender
* Aged between 8 and 18 years
* Have a baseline FEV1 of \<70% of the predicted normal value
* Currently taking rhDNase for at least 4 weeks

Exclusion Criteria:

* Currently active asthma, uncontrolled hypertension, colonised with Burkholderia cepacia or MRSA
* Listed for transplantation
* Known intolerance to mannitol, rhDNase or bronchodilators

Answer: C