Clinical trial NCT00455130: A Phase 2 Study to Determine the Safety and Efficacy of Inhaled Dry Powder Mannitol in Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Keywords: mannitol
cystic fibrosis
mucolytic
mucoactive
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2007-04-03
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Cystic fibrosis is the most frequent lethal genetic disease of childhood. Causes disruption of glandular function of the pancreas, intestine, liver, lungs (causing chronic lung infection with emphysema), sweat glands and reproductive organs. We know that many CF patients die of lung failure, brought about in part by repeated lung infections caused by thick, sticky mucus that cannot be readily cleared from the lung.

Inhaled mannitol is an osmotic agent that has been investigated in a number of small studies that have examined mucociliary clearance, quality of life and lung function in CF and bronchiectasis. The promising results of these studies warrant futher investigation. The aim of this study is to assess the safety and efficacy of inhaled mannitol when administered twice a day over two weeks in CF.


Eligibility criteria: 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

Primary outcomes:
measure: FEV1
Secondary outcomes:
measure: Other measures of lung function
measure: Quality of life
measure: Sputum microbiology
measure: Sputum rheology
measure: Safety
Other outcomes:
Locations:
city: Sydney
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Sydney
country: Australia
facility: Childrens Hospital at Westmead
state: New South Wales
city: Brisbane
country: Australia
facility: Prince Charles Hospital
state: Queensland
city: Melbourne
country: Australia
facility: Royal Children's Hospital
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Perth
country: Australia
facility: Princess Margaret Hospital for Children
state: Western Australia
city: Perth
country: Australia
facility: Sir Charles Gairdner
state: Western Australia
city: Auckland
country: New Zealand
facility: Greenlane Hospital
state: North Island
Study officials:
affiliation: Syntara
name: Brett Charlton
role: STUDY_DIRECTOR
References:
citation: Jaques A, Daviskas E, Turton JA, McKay K, Cooper P, Stirling RG, Robertson CF, Bye PTP, LeSouef PN, Shadbolt B, Anderson SD, Charlton B. Inhaled mannitol improves lung function in cystic fibrosis. Chest. 2008 Jun;133(6):1388-1396. doi: 10.1378/chest.07-2294. Epub 2008 Mar 13.
citation: Daviskas E, Anderson SD, Jaques A, Charlton B. Inhaled mannitol improves the hydration and surface properties of sputum in patients with cystic fibrosis. Chest. 2010 Apr;137(4):861-8. doi: 10.1378/chest.09-2017. Epub 2009 Oct 31.