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Trial registered on ANZCTR


Trial ID
ACTRN12617001356358
Ethics application status
Approved
Date submitted
11/09/2017
Date registered
27/09/2017
Date last updated
27/09/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Assessment of inflammatory characteristics and cell function with changes in asthma control
Scientific title
Assessment of asthma phenotype and airway neutrophil function after changes in asthma control/medication in adult asthmatics
Secondary ID [1] 292850 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 304693 0
Condition category
Condition code
Respiratory 304003 304003 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A group of adult asthmatics (recruited through general practice and advertisement) will be asked if they are amenable to a tailored change in their current asthma treatment. Change in treatment will be made on an individual basis by the supervising clinician according to the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 (EPR 3) guidelines, in which asthma control status is based on asthma control questionnaire (ACQ) 7 score, An ACQ-7 score <0.75 will be considered adequately controlled, ACQ-7 >1.5 will be considered inadequately controlled. Once asthma control status/treatment has been ascertained, participants will undergo a clinical assessment (including sputum induction).
Group 1: Subjects with adequately controlled asthma (as determined on initial visit) will have their current treatment sub-optimised to a reduced dose of their currently used inhaled corticosteroids (ICS) or to no ICS. The reduction in ICS dose will discussed and agreed with the participant, and will be between 250-1000 mcg budesonide equivalent dose per day. They will then be monitored over a 4-6 week period by weekly review appointments and phone calls (as required) with the supervising physician to assess symptoms, lung function, adherence to ICS dose, and loss of control (based on the criteria of Jone SL et al, Am J Resp Crit Care Med 2001; 164; 738-743). Briefly, this includes the onset of distressing or intolerable asthma symptoms, night wakening with asthma symptoms on more than 3 nights per week, or increase in bronchodilator use of >3 puffs daily. After the 4-6 week period, participants will undergo a further clinical assessment (including sputum induction).

Group 2: Subjects with inadequately controlled asthma (as determined on initial visit) will have their treatment optimised and either commence ICS use or increase their current ICS dose. The increase in ICS dose will discussed and agreed with the participant, and will be between 250-1000 mcg budesonide equivalent dose per day. They will then be monitored over a 4-6 week period by weekly review appointments and phone calls (as required) with the supervising physician to assess symptoms, lung function, adherence to ICS dose, and changes in asthma control (as described for group 1), and then undergo a further clinical assessment (including sputum induction).

As this is a pilot/feasibility study, the duration between assessments (4-6 weeks) will be flexible and based on the availability of both participant and research team. All participants will continue to use short-acting beta-agonists (SABA) as required, and at the end of the study/time of the second sputum induction, asthma treatment will be adjusted for all subjects according to their asthma control.
Intervention code [1] 299095 0
Treatment: Drugs
Comparator / control treatment
All asthmatic participants will undergo assessment at a period in which there asthma is considered adequately controlled and inadequately controlled by the supervising physician, and therefore act as their own control (crossover),
A group of non-asthmatic participants will also undergo clinical assessment (with no intervention) as a comparator group for groups 1 and 2 for airway inflammatory characteristics.
Control group
Active

Outcomes
Primary outcome [1] 303332 0
To assess if change in asthma treatment/control is associated with a change in the percentage of leukocyte populations in induced sputum, as determined by differential cell count and light microscopy.
Timepoint [1] 303332 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.
Primary outcome [2] 303333 0
To assess if change in asthma treatment/control is associated with change in airway neutrophil cell functional parameters (alteration in respiratory burst/dihydrorhodamine 123 staining) as assessed by flow cytometry,
Timepoint [2] 303333 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.
Primary outcome [3] 303432 0
To assess if change in asthma treatment/control is associated with change in airway neutrophil cell functional parameters (alteration in phagocytic activity/zymosan A-texas red bead uptake) as assessed by flow cytometry,
Timepoint [3] 303432 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.
Secondary outcome [1] 338667 0
To assess if a change in asthma treatment/control is associated with a change in lung function parameters. These will include FEV1, FVC, FEV1/FVC, and will be measured using an Easyone spirometer.
Timepoint [1] 338667 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.
Secondary outcome [2] 338922 0
To assess if a change in asthma treatment/control is associated with a change in numbers and phenotype of airway inflammatory cells (using flow cytometry) and levels of soluble mediators in sputum supernatant (using ELISA). These outcomes are for assessment of method feasibility.
Timepoint [2] 338922 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.
Secondary outcome [3] 338923 0
To assess if a change in asthma treatment/control is associated with a change in exhaled nitric oxide (FENO) levels. This will be measured using a Medisoft Hypair analyser according to ATS/ERS guidelines.
Timepoint [3] 338923 0
4-6 weeks after initiating change in treatment. As this is a pilot/feasibility study, and we are interested in the difference in outcomes between adequately controlled and inadequately controlled asthma rather than the effect of treatment per se, the duration between assessments will be flexible and based on the availability of both participant and research team.

Eligibility
Key inclusion criteria
Inclusion criteria for asthmatics:
physicians diagnosis of asthma, history of wheeze in last 12 months or asthma medication use in the last 12 months, FEV1>75% predicted,
Inclusion criteria for non-asthmatics:
No previous or current diagnosis of asthma, no history of wheeze or nocturnal cough in the last 12 months, FEV1>75% predicted.
Minimum age
17 Years
Maximum age
65 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Both asthmatics and non-asthmatics:
Respiratory tract infection/symptoms in the 4 weeks preceding recruitment, a history of chronic or immune system disease other than asthma, FEV1<75% predicted,

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Change in treatment is to be made on an individualised basis by the supervising physician according to the National Asthma Education and Prevention Program (NAEPP) Expert Panel Report 3 (EPR 3) guidelines.
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis
This study is considered a pilot study, and the number of participants is based on what we have found feasible in previous studies of airway inflammation.
Data will be analysed using the paired t-test or Wilcoxon’s matched pairs test as appropriate. Fisher’s exact test will be used for categorical data, and Kruskal-Wallis with Dunn’s post-test analysis will be used for multiple group comparison.
Data will initially be analysed separately for asthmatics in groups 1 and 2. Subsequently, data will be combined to increase power and allow comparison of the two visits for all asthmatic participants when considered adequately controlled/inadequately controlled. As it has been suggested that different asthma phenotypes have distinct pathologies and response to ICS and that neutrophils may be particularly important in NEA, further analyses will be conducted to assess differences associated with change in treatment in asthmatics characterised as EA/NEA (EA defined as having 2% or greater sputum eosinophils at either assessment).

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 outside Australia
Country [1] 9188 0
New Zealand
State/province [1] 9188 0
Wellington

Funding & Sponsors
Funding source category [1] 297483 0
Charities/Societies/Foundations
Name [1] 297483 0
Asthma and Respiratory Foundation (New Zealand)
Address [1] 297483 0
The Woolstore
262 Thorndon Quay
Pipitea,
Wellington 6011
Country [1] 297483 0
New Zealand
Primary sponsor type
University
Name
Centre for Public Health Research, Massey University.
Address
Wellington Campus
PO Box 756
Wellington 6140
Country
New Zealand
Secondary sponsor category [1] 296480 0
None
Name [1] 296480 0
Address [1] 296480 0
Country [1] 296480 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298585 0
Lower South Ethics Committee
Ethics committee address [1] 298585 0
Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 298585 0
New Zealand
Date submitted for ethics approval [1] 298585 0
01/07/2010
Approval date [1] 298585 0
01/09/2010
Ethics approval number [1] 298585 0
LRS/10/07/031

Summary
Brief summary
Asthma inflammatory phenotypes are often defined by relative cell counts of airway eosinophils/neutrophils. However, the importance of neutrophilia remains unclear, as does the effect of ICS treatment on asthma phenotypes and airway neutrophil function. The purpose of this study was to determine how treatment changes affect phenotype stability and inflammation, with particular focus on airway neutrophils.
Trial website
Trial related presentations / publications
None
Public notes
This study (designed to recruit 30 asthmatics and 15 non-asthmatics), was developed to assess functional and inflammatory characteristics of asthma at different stages of control. To this end, changes in asthma management will be implemented. It was not developed to determine the efficacy, pharmacokinetics, toxicity, etc. of inhaled corticosteroids,

Contacts
Principal investigator
Name 77562 0
Dr Collin Brooks
Address 77562 0
Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140
Country 77562 0
New Zealand
Phone 77562 0
+64-4-3800609
Fax 77562 0
+64-4-8027120
Email 77562 0
c.r.brooks@massey.ac.nz
Contact person for public queries
Name 77563 0
Dr Collin Brooks
Address 77563 0
Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140
Country 77563 0
New Zealand
Phone 77563 0
+64-4-3800609
Fax 77563 0
+64-4-8027120
Email 77563 0
c.r.brooks@massey.ac.nz
Contact person for scientific queries
Name 77564 0
Dr Collin Brooks
Address 77564 0
Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140
Country 77564 0
New Zealand
Phone 77564 0
+64-4-3800609
Fax 77564 0
+64-4-8027120
Email 77564 0
c.r.brooks@massey.ac.nz