Clinical trial NCT00251056: Mannitol Dose Response Study in Cystic Fibrosis
Official title: A Phase IIa Randomised, Open Label, Dose Response Study to Determine the Optimum Dose of Dry Powder Mannitol Required to Generate Clinical Improvement In Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cystic Fibrosis
Lead sponsor: Syntara
Sponsor class: INDUSTRY
First posted: 2005-11-09
Enrollment: 48
Sex: ALL
Minimum age (years): 7
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Many cystic fibrosis patients die of lung failure caused by repeated lung infections from thick, sticky mucus. Past studies have shown Bronchitol inhalation may help to facilitate the clearance of mucus by altering its rheology and replenishing the airway surface liquid layer in these patients, thereby enhancing the shift of stagnant mucus from the lungs. The study aim is to determine the optimal dose of mannitol to generate clinical improvement in patients with cystic fibrosis.


Eligibility criteria: Inclusion Criteria:

* Diagnosis of cystic fibrosis (sweat test/genotype)
* 7 years or older
* FEV1 between 40% and 90% of predicted for height, age and gender.
* Able to perform acceptable-quality spirometry
* Clinically stable in the week up to study entry
* No additional antibiotics or additional oral steroids for a period of 14 days before study entry (routine antibiotics permitted)

Exclusion Criteria

* Currently active asthma
* Subjects colonized with Burkholderia cepacia or MRSA
* Considered "terminally ill" or listed for transplantation
* Requiring home oxygen or assisted ventilation
* Concurrent illness that in the investigators opinion may contribute to an increased and unacceptable risk if the subject was enrolled in the study (e.g. significant varicies, portal hypertension, cor pulmonale)
* Significant episode of haemoptysis (\>60 mLs) in the previous 12 months
* Heart attack or stroke in last 3 months
* Known aortic or cerebral aneurysm
* Subjects who are breast feeding or pregnant.
* At risk females unwilling to use appropriate contraception to prevent pregnancy during the course of the study
* Subjects who have participated in another investigative drug study parallel to, or within 4 weeks of study entry.
* Known intolerance to mannitol or unable to take any form of bronchodilator medications.
* Uncontrolled hypertension, systolic BP \> 200 or diastolic BP\> than 100
* Concurrent use of beta blocker medication
* Concurrent use of hypertonic saline

Canada:

* Concurrent use of other pharmacological mucolytic agents other than Pulmozyme

Argentina:

* Concurrent use of other pharmacological mucolytic agents including Pulmozyme

Primary outcomes:
measure: FEV1
timeFrame: 2 weeks
measure: FVC
timeFrame: 2 weeks
Secondary outcomes:
measure: other measures of lung function
timeFrame: various
measure: QOL
timeFrame: 2 weeks
measure: sputum microbiology
timeFrame: 2 weeks
measure: safety
timeFrame: 2 weeks
measure: sputum clearance and cough
timeFrame: 2 weeks
measure: respiratory symptoms
timeFrame: 2 weeks
Other outcomes:
Locations:
city: La Plata
country: Argentina
facility: Hospital de Niños Superiora Sor María Ludovica
state: Buenos Aires
city: Resistencia
country: Argentina
facility: Hospital Pediatrico
state: Chaco
city: Buenos Aires
country: Argentina
facility: Hospital Interzonal Especializado Materno Infantil (HIEMI)
city: Caba
country: Argentina
facility: Hospital General de Niños
city: Mendoza
country: Argentina
facility: Hospital Pediatrico Dr Humberto J Notti
city: Vancouver
country: Canada
facility: BC Children's Hospital
state: British Columbia
city: Vancouver
country: Canada
facility: St Pauls Hospital
state: British Columbia
city: St Johns
country: Canada
facility: Janeway Children's Health and Rehabilitation Center
state: Newfoundland and Labrador
city: Halifax
country: Canada
facility: Queen Elizabeth II Health Sciences Centre
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Toronto
country: Canada
facility: The Hospital for Sick Children
state: Ontario
city: Toronto
country: Canada
facility: St Michaels Hospital
state: Ontario
Study officials:
affiliation: St Michaels Hospital, Toronto, Ontario, Canada
name: Elizabeth Tullis, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pharmaxis Ltd, Sydney, NSW, Australia
name: Brett Charlton, MBBS PhD
role: STUDY_DIRECTOR
References: