ANZCTR - Registration

Registration number

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]

None

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Asthma

Condition category

Condition code

Respiratory

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

Sex

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

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

1/09/2010

Date of last participant enrolment

Anticipated

Actual

8/08/2011

Date of last data collection

Anticipated

Actual

10/08/2011

Sample size

Target

45

Accrual to date

Final

45

Recruitment outside Australia

Country [1]

New Zealand

State/province [1]

Wellington

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Asthma and Respiratory Foundation (New Zealand)

Country [1]

New Zealand

Primary sponsor type

University

Name

Centre for Public Health Research, Massey University.

Country

New Zealand

Secondary sponsor category [1]

None

Name [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Lower South Ethics Committee

Ethics committee address [1]

Health and Disability Ethics Committees
Ministry of Health
Freyberg Building
20 Aitken Street
PO Box 5013
Wellington 6011

Ethics committee country [1]

New Zealand

Date submitted for ethics approval [1]

01/07/2010

Approval date [1]

01/09/2010

Ethics approval number [1]

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

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

Dr Collin Brooks

Address

Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140

Country

New Zealand

Phone

+64-4-3800609

Email

[email protected]

Contact person for public queries

Name

Collin Brooks

Address

Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140

Country

New Zealand

Phone

+64-4-3800609

Email

[email protected]

Contact person for scientific queries

Name

Collin Brooks

Address

Centre for Public Health Research
Massey University
Wellington Campus
PO Box 756
Wellington 6140

Country

New Zealand

Phone

+64-4-3800609

Email

[email protected]

Trial Review

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