Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000985583
Ethics application status
Approved
Date submitted
13/08/2015
Date registered
22/09/2015
Date last updated
28/11/2018
Date data sharing statement initially provided
28/11/2018
Date results information initially provided
28/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Relationship between neutrophils, airway function and remodelling in older people with asthma.
Scientific title
Using lung function tests and bronchoscopy to determine the relationship between neutrophils, airway function and remodelling in older people with asthma.
Secondary ID [1] 284529 0
Nil
Universal Trial Number (UTN)
U1111-1156-2795
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 291785 0
Condition category
Condition code
Respiratory 292150 292150 0 0
Asthma

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Subjects with asthma will undergo breathing tests, allergy tests and a bronchoscopy. The breathing tests will include spirometry, lung volumes, DLCO, methacholine challenge, exhaled nitric oxide, multiple breath nitrogen wash out, forced oscillation technique and lung elastic recoil. The breathing tests will involve the subject breathing into a mouth piece attached to different machines. During the methacholine challenge, an aerosol of methacholine will be inhaled to look at how sensitive the airways are. During the lung elastic recoil test a fine flexible tube with a latex balloon attached at the end, will be passed through the nose down to the oesophagus (with local anaesthetic, 1.5ml Xylocaine viscous, applied to the nostrils prior) to test the elasticity of the lungs. A skin prick test will be used to test for allergies. The bronchoscopy involves placing a bronchoscope (thin flexible tube-like instrument with a mini camera at its tip) through the nose or mouth into the lungs to allow us to look into the airways. Local anaesthetic and sedating medications will be used prior to the bronchoscopy. The local anaesthetic (10% Xylocaine) will be applied topically to each nostril (1 spray each) and to the back of the throat (1 spray) 5-10 minutes before the procedure. Sedation will be administered intravenously (0.5-5mg diazepam +/- 12.5-100mcg fentanyl) before the procedure. Further local anaesthetic (1% Xylocaine) will be applied to the vocal cords and to the airways in 2.5 ml aliquots via the bronchoscope channel (maximum dose 4-5 mg/kg). During the bronchoscopy small samples from the lining of lung will be taken and fluid (sterile saline) will be flushed down the bronchoscope. This fluid will be sucked back up the bronchoscope and cells in the fluid will be analysed. A blood test will be taken at the time of the bronchoscopy and this will also be analysed.

The study will involve 4 visits (3 visits for breathing tests and 1 visit for the bronchoscopy). The breathing tests will take place at the start of the study, 1 month and 2 months after recruitment. The first and last visit for breathing tests will take up to 4 hours. The second visit for breathing tests will take up to an hour. The bronchoscopy will be performed 2 months after recruitment and will take up to 6 hours.
Intervention code [1] 290267 0
Not applicable
Comparator / control treatment
No control arm
Control group
Uncontrolled

Outcomes
Primary outcome [1] 293182 0
Relationship between neutrophil elastase and matrix metalloproteinase-9 levels (from blood and peripheral airways), peripheral airway function (the parameters Sacin and Scond derived from the mulitple nitrogen wash out test) and lung elastic recoil.
Timepoint [1] 293182 0
Two months after recruitment
Secondary outcome [1] 310538 0
Neutrophil function in the peripheral airways and blood. Neutrophil function will be assessed by comparing the basal and stimulated release of the neutrophil chemokines (CXCL8, CXCL1) and assessing their lifespan in-vitro.
Timepoint [1] 310538 0
Two months after recruitment.
Secondary outcome [2] 317360 0
The effects of neutrophils on airway extra cellular matrix (ECM). The effects of neutrophil products on ECM will be performed by assessing the breakdown of ECM and elastin, mesenchymal cell proliferation and ECM production.
Timepoint [2] 317360 0
Two months after recruitment.

Eligibility
Key inclusion criteria
Doctor diagnosis of asthma.
Age > 40 years.
Non smoker (no smoking for > 6 months and < 10 pack/year smoking history).
Minimum age
40 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Other significant cardiac or pulmonary diseases.
Using regular oral corticosteroid medication.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Aim 1: To correlate neutrophil elastase with peripheral airway function (Sacin) and lung elastic recoil

Previous research in this lab found neutrophil elastase from sputum to be related to Sacin (r=0.61, p=0.003, n=17). Assuming a similar relationship with an r=0.5, 28 subjects would be required for a power of 80% at the 0.05 level of significance.

Aim 2(a): To correlate neutrophil function (by the release of it's enzymes neutrophil elastase and MMP-9) with peripheral airway function

Previous research in this lab has shown neutrophil elastase levels after stimulation with FMLP were 1.2 vs 2.2 units (SD 4.3 units) in severe vs non-severe asthmatics. Assuming similar differences, 38 subjects will be required for 80% power at the 0.05 level of significance.

Aim 2(b): To correlate neutrophil effects on the extra cellular matrix in people with asthma who do and do not have peripheral airway dysfunction

38 subjects will be required to complete the study. Allowing a 10% dropout and at least 1/3 agreeing to perform all the tests, 126 subjects will be screen to enrol 38 subjects.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
21/09/2015
Actual
22/10/2015
Date of last participant enrolment
Anticipated
Actual
31/12/2016
Date of last data collection
Anticipated
Actual
28/02/2017
Sample size
Target
38
Accrual to date
Final
23
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 2987 0
Concord Repatriation Hospital - Concord
Recruitment hospital [2] 2988 0
Royal North Shore Hospital - St Leonards
Recruitment hospital [3] 2989 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 2990 0
Macquarie University Hospital - Macquarie Park
Recruitment postcode(s) [1] 8711 0
2050 - Missenden Road
Recruitment postcode(s) [2] 8710 0
2065 - Royal North Shore Hospital
Recruitment postcode(s) [3] 8712 0
2109 - Macquarie University
Recruitment postcode(s) [4] 8709 0
2139 - Concord Repatriation Hospital

Funding & Sponsors
Funding source category [1] 289964 0
University
Name [1] 289964 0
Australian Post Graduate Award
University of Sydney
Country [1] 289964 0
Australia
Funding source category [2] 289965 0
University
Name [2] 289965 0
University of Sydney Bridging Grant
Country [2] 289965 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Woolcock Institute of Medical Research
Address
431 Glebe Point Rd
Glebe NSW 2037
Country
Australia
Secondary sponsor category [1] 288655 0
None
Name [1] 288655 0
Address [1] 288655 0
Country [1] 288655 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 291677 0
Sydney Local Health District HREC - CRGH
Ethics committee address [1] 291677 0
Concord Hospital
Hospital Rd
Concord NSW 2139
Ethics committee country [1] 291677 0
Australia
Date submitted for ethics approval [1] 291677 0
Approval date [1] 291677 0
27/08/2014
Ethics approval number [1] 291677 0
HREC/14/CRGH/75

Summary
Brief summary
Fixed airway narrowing is a common complication of long standing asthma. It occurs despite good treatment with puffers that are effective in controlling inflammation. It causes symptoms such as wheeze, cough, shortness of breath and there is no known treatment for asthma related fixed airway narrowing because the mechanisms and causes are poorly understood. It is more common in older patients who have had asthma for many years, in whom there are also greater symptoms.

Airway inflammation due to neutrophils is more common in older people with asthma who have fixed airway narrowing. Neutrophils are a type of cell that are part of the body's immune system which causes inflammation. Neutrophilic airway inflammation can cause damage to the airways and lung tissue. The aim of this research is to determine how neutrophils affect the function of the smaller airways in older people with asthma. We will also determine how neutrophils cause airway and lung damage, which can lead to fixed airway narrowing.

We will recruit people with asthma who are >40 years of age, are non smokers and have no other significant lung or heart problems. Participants will undergo breathing tests and a bronchoscopy, using a small camera on the end of a flexible tube, to obtain samples from their lungs.

The significance of this study will be the discovery of the mechanisms that underlies this major complication of asthma. It will assist in overcoming the major barrier halting progress to an effective treatment strategy for which the mechanisms are unknown.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48058 0
Dr Claude Farah
Address 48058 0
Respiratory Department
Level 7 West
Concord Hospital
Hospital Road
Concord NSW 2139
Country 48058 0
Australia
Phone 48058 0
+61297676712
Fax 48058 0
Email 48058 0
claude.farah@sydney.edu.au
Contact person for public queries
Name 48059 0
Katrina Tonga
Address 48059 0
Woolcock Institute of Medical Research
431 Glebe Point Rd
Glebe NSW 2037
Country 48059 0
Australia
Phone 48059 0
+61291140148
Fax 48059 0
Email 48059 0
katrina.tonga@sydney.edu.au
Contact person for scientific queries
Name 48060 0
Katrina Tonga
Address 48060 0
Woolcock Institute of Medical Research
431 Glebe Point Rd
Glebe NSW 2037
Country 48060 0
Australia
Phone 48060 0
+61291140148
Fax 48060 0
Email 48060 0
katrina.tonga@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Confidential patient information


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually

Documents added automatically
No additional documents have been identified.