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Trial registered on ANZCTR


Registration number
ACTRN12605000473662
Ethics application status
Approved
Date submitted
15/09/2005
Date registered
23/09/2005
Date last updated
10/12/2018
Date data sharing statement initially provided
10/12/2018
Date results information initially provided
10/12/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Mannitol and nasal mucociliary clearance
Scientific title
A randomised, double-blind, placebo controlled trial of the effect versus placebo of twice daily doses of mannitol (80mg) for one week on nasal mucociliary clearance in healthy adults and adults with allergic rhinitis or chronic sinusitis.
Universal Trial Number (UTN)
Trial acronym
MCC123
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Rhinosinusitis 593 0
Allergic Rhinitis 594 0
Condition category
Condition code
Respiratory 666 666 0 0
Other respiratory disorders / diseases
Inflammatory and Immune System 667 667 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A double-blind cross-over placebo controlled system will be used. Computer generated randomisation will be conducted internally by a non-study related third party. Patients will be randomly assigned to receive either mannitol first and then placebo, or placebo first and then mannitol. There will be a one-week washout period between treatments. At the same time each morning and evening (approx. 12 h apart) for one week, subjects will be required to intranasally apply one actuation (40 mg) of either mannitol (contained within a gelatin capsule) or placebo (gelatin capsule containing 40mg lactose) to each nostril using a dry powder inhaler device (Teijen spray applicator). All capsules will be weighed prior to and after each inhalation to check compliance and to determine the actual amount of mannitol delivered.
Intervention code [1] 616 0
Other interventions
Comparator / control treatment
Placebo (gelatin capsule containing 40mg lactose)
Control group
Placebo

Outcomes
Primary outcome [1] 792 0
The mucociliary clearance rate will be measured using the radiolabeled aerosol tracer method which is a previously established method for measurement of mucociliary clearance rates. The same nasal cavity side will be used for each assessment.
Timepoint [1] 792 0
Measurements will made immediately prior to the inhalation of the first dose of mannitol or placebo (single baseline reading) and then 1 hour after the first dose of mannitol /placebo and 12 hours after the last dose of mannitol/placebo, after a weeks' treatment. All of these readings will be taken in the morning.
Secondary outcome [1] 1608 0
Nasal/ocular symptom scores:
Patients will record the presence and severity of nasal symptoms in the morning and evening for one week before the study commences (baseline reading) and then 1 h after each dose of mannitol/placebo using a categorical scoring system. This scoring system requires subjects to assess the severity of their symptoms by assigning scores for sneezing, rhinorrhoea, blockage and itching on a graded scale from 0 to 3. The maximum achievable score for nasal symptoms is therefore 12. Twice-daily assessments of ocular symptoms including the severity of watering, itching and redness will also be made. Each symptom will be scored out of 3 and summed to give a maximum total score of 9.
Timepoint [1] 1608 0
Secondary outcome [2] 1609 0
Nasal patency:
Domiciliary peak nasal inspiratory flow (PNIF) rates will be measured twice each day, 1 h after the inhalation of mannitol/placebo, using an In-Check portable nasal inspiratory flow meter (Clement Clarke International, Harlow, Essex, UK). These will be recorded in a dairy card. Only the highest recorded measurement will be used in the final analyses.
Timepoint [2] 1609 0
Secondary outcome [3] 1610 0
Quality of Life:
A validated and standardized, rhinoconjunctivitis quality of life questionnaire (RQLQ) will be administered to all subjects both before, and at the end of the placebo and treatment arms of the study. In addition, subjects with chronic rhinosinusitis will be required to complete the 20-item sino-nasal outcome test (SNOT-20) both before, and at the end of the placebo and treatment arms of the study.
Timepoint [3] 1610 0

Eligibility
Key inclusion criteria
All subjects must: be able to give written, informed consent; be willing, able and likely to complete the study including compliance with study procedures and restrictions; be able to read, comprehend and record information in English; be between 18 and 70 years of age at first visit; be non-smokers. Only females >55 years of age who have not had a menstrual period in the last 12 months or females <55 years of age who have not had a menstrual period in the past 12 months and who have had their post-menopausal condition confirmed by laboratory blood test, will be eligible to participate.
In addition, all subjects must withhold the following medications prior to and for the duration of the study: intranasal steroids, 2 weeks; oral or intranasal antihistamines, 48 h; intranasal decongestants, 24 h.Healthy subjects: Must have no upper or lower respiratory diseases or disorders; no current symptoms of allergic rhinitis or chronic sinusitis; no history of allergic rhinitis or chronic sinusitis; no severe physical obstruction of the nose (i.e. deviated septum or nasal polyps).Persistent allergic rhinitis subjects: Must have a positive skin prick test response to a perennially-occurring allergen (animal dander, house dust mite, cockroach, mould) within the last 12 months; have nasal symptoms that are present for more than 4 days a week and for more than 4 weeks per year (current definition of persistent allergic rhinitis)[15].Chronic rhinosinusitis: Must have had symptoms continuously present for >12 weeks; must present with 2 or more major factors or 1 major and at least 2 minor factors from the following lists; Major: facial pain/pressure nasal blockage, nasal discharge/purulence/ discoloured postnasal drainage, hyposmia/anosmia; purulence in nasal cavity on examination. Minor: headache, fever, halitosis, fatigue, dental pain, cough, ear pain/pressure/fullness[16]. An abnormal CT scan will be required to confirm the diagnosis. Previous surgery does not exclude the subject so long as the latest CT scan is abnormal.
Minimum age
18 Years
Maximum age
Not stated
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Current asthmatics will be excluded from the study and all subjects will have a baseline FEV1 which is >70% predicted.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
The allocation of medications is blind and the randomisation schedule is stored in a sealed envelope
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The sequence was generated by tossing a coin.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 3
Type of endpoint(s)
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)

Funding & Sponsors
Funding source category [1] 735 0
Commercial sector/Industry
Name [1] 735 0
Pharmaxis
Address [1] 735 0
Country [1] 735 0
Australia
Primary sponsor type
Other
Name
Woolcock Institute of Medical Research
Address
Country
Australia
Secondary sponsor category [1] 609 0
None
Name [1] 609 0
Not applicable
Address [1] 609 0
Country [1] 609 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 1929 0
University of Sydney Ethics Committee
Ethics committee address [1] 1929 0
Ethics committee country [1] 1929 0
Australia
Date submitted for ethics approval [1] 1929 0
Approval date [1] 1929 0
01/06/2005
Ethics approval number [1] 1929 0
Ethics committee name [2] 1930 0
Royal North Shore Hospital
Ethics committee address [2] 1930 0
Ethics committee country [2] 1930 0
Australia
Date submitted for ethics approval [2] 1930 0
Approval date [2] 1930 0
Ethics approval number [2] 1930 0

Summary
Brief summary
Trial website
Trial related presentations / publications
None known
Public notes

Contacts
Principal investigator
Name 35873 0
Address 35873 0
Country 35873 0
Phone 35873 0
Fax 35873 0
Email 35873 0
Contact person for public queries
Name 9805 0
Ms Wendy Taylor
Address 9805 0
Woolcock Institute of Medical Research
PO Box M77
Missenden Road
Camperdown NSW 2050
Country 9805 0
Australia
Phone 9805 0
+61 2 95156578
Fax 9805 0
+61 2 95505865
Email 9805 0
volunteers@woolcock.org.au
Contact person for scientific queries
Name 733 0
Ms Melanie Lean
Address 733 0
Woolcock Institute of Medical Research
PO Box M77
Missenden Road
Camperdown NSW 2050
Country 733 0
Australia
Phone 733 0
+61 2 93514145
Fax 733 0
+61 2 93517451
Email 733 0
melaniel@woolcock.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary