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Trial registered on ANZCTR


Registration number
ACTRN12620001159943
Ethics application status
Approved
Date submitted
29/06/2020
Date registered
4/11/2020
Date last updated
4/11/2020
Date data sharing statement initially provided
4/11/2020
Type of registration
Retrospectively registered

Titles & IDs
Public title
MRI for investigating airway clearance techniques in adults with cystic fibrosis
Scientific title
The use of novel magnetic resonance imaging techniques to investigate lung structure and ventilation pre- and post-airway clearance techniques in adults with cystic fibrosis
Secondary ID [1] 301649 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cystic fibrosis 318062 0
Condition category
Condition code
Respiratory 316097 316097 0 0
Other respiratory disorders / diseases
Human Genetics and Inherited Disorders 316392 316392 0 0
Cystic fibrosis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single visit, proof of concept study investigating the use of a novel outcome measure (magnetic resonance imaging [MRI]) to measure changes in lung structure and ventilation following airway clearance techniques in adults with CF. Each participant will complete three MRI scans (each lasting approximately 20 minutes): firstly at the commencement of the visit, then after airway clearance techniques or washout period (25 minutes) and then again after airway clearance techniques or washout period (25 minutes), conducted in randomised order (i.e. one period of airway clearance and one washout period per participant in a randomised order). The total study visit is expected to last no more than 2 hours. The participant will complete their usual airway clearance technique, supervised by an experienced CF physiotherapist. The MRI scans will be completed by an experienced MRI technician.
Intervention code [1] 317953 0
Treatment: Other
Comparator / control treatment
The participant is being used as their own comparator/control during the washout period in the study design. During this period, the participant will sit in a quiet room and be instructed to breathe normally/rest.
Control group
Active

Outcomes
Primary outcome [1] 324292 0
1) Lung structure

We will use a version of the PRAGMA-CF scoring system (widely used in CF CT scan studies), adapted for use in MRI, for assessment of structural lung abnormalities.15 In brief, PRAGMA-CF involves overlaying a square grid over the MRI images and annotating grid cells for the presence of CF-related structural lung disease. The total proportion of the lung with disease, %Disease, is reported and represents the extent of structural disease. Additionally, the extent of mucus plugging, %MucusPlugging, will be reported.
Timepoint [1] 324292 0
On day of MRI
Primary outcome [2] 325298 0
2) Lung ventilation

The same PRAGMA-CF process will be used to determine the severity of hypoventilation in the lung, from the Fourier Decomposition scans (%Hypoventilated).
Timepoint [2] 325298 0
On day of MRI
Secondary outcome [1] 384262 0
Nil
Timepoint [1] 384262 0
Nil

Eligibility
Key inclusion criteria
Diagnosis of CF; aged 18 years or older; under the care of the SCGH CF team; no signs of a respiratory exacerbation in the preceding four weeks.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previous lung transplantation; inability to perform ACT; inability to expectorate mucus; type 1 respiratory failure requiring supplemental oxygen therapy; pneumothorax in the previous 3 months; current haemoptysis; pregnancy; failing to comply with standardised pre-MRI safety checklists; potential intolerance to MRI environment due to severe claustrophobia.

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
All scans will be retrieved and de-identified before analysis. Assessment of MRI scans will be performed in random order, blinded to clinical and research outcomes. The PRAGMA-CF scoring system, adapted for use in MRI, for assessment of structural lung abnormalities. This involves overlaying a square grid over the MRI images and annotating grid cells for the presence of CF-related structural lung disease. This will be performed by a scientist blinded to group allocation, who is experienced in using this scoring system.

The total proportion of the lung with disease, %Disease, is reported and represents the extent of structural disease. Additionally, the extent of mucus plugging, %MucusPlugging, will be reported. The same process will be used to determine the severity of hypoventilation in the lung, from the Fourier Decomposition scans (%Hypoventilated).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
30/06/2020
Date of last participant enrolment
Anticipated
18/12/2020
Actual
Date of last data collection
Anticipated
18/12/2020
Actual
Sample size
Target
12
Accrual to date
8
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 16991 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 30655 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 306082 0
Hospital
Name [1] 306082 0
Sir Charles Gairdner Hospital
Country [1] 306082 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue, Nedlands, Western Australia 6009
Country
Australia
Secondary sponsor category [1] 306547 0
None
Name [1] 306547 0
Address [1] 306547 0
Country [1] 306547 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306303 0
Sir Charles Gairdner and Osborne Park Health Care Group Human Research Ethics Committee
Ethics committee address [1] 306303 0
Hospital Avenue, Nedlands, Western Australia 6009
Ethics committee country [1] 306303 0
Australia
Date submitted for ethics approval [1] 306303 0
29/10/2019
Approval date [1] 306303 0
31/05/2020
Ethics approval number [1] 306303 0

Summary
Brief summary
We aim to investigate new techniques in magnetic resonance imaging (MRI) pre and post airway clearance techniques (ACT). Adults with CF will be invited to participate, and to perform their usual ACT (i.e. breathing exercises to clear mucus from their airways) within the MRI under the guidance of an experienced physiotherapist. This will allow for innovative cutting edge imaging to be performed before and after the ACT are performed, to provide information on airway structure and function; specifically in regard to the movement of mucous (sputum) and trapped air, and well as dynamic function of the larger airways.

This is important, as ACT are one of the cornerstone daily treatments undertaken in CF, yet to date no modern ACT has been shown to be superior, largely due to limited outcome measures. While lung imaging is appealing, until recently only computed tomography (CT) has been available to provide the necessary imaging. Unfortunately, CT exposes the patient to ionising radiation exposure which limits its use for especially functional imaging. Using MRI provides avoids radiation risk, therefore is an excellent option for structure and function imaging in relation to ACT. This is the first study of its kind, utilising novel MRI techniques.

The experienced and capable research team will investigate the use of novel MRI techniques to objectively quantify lung structure and ventilation during ACT in adults with CF, providing new data in this area to assist in the understanding of ACT in the future. The MRI techniques used have the potential to also be used in other lung diseases such as bronchiectasis, COPD and asthma, and therefore this study is the beginning of a much larger research focus in this field.

Aims

In adults with CF:

1) Establish a protocol for the use of MRI to detect changes in lung structure and ventilation in relation to mucus movement during ACT;

2) Conduct a series of three MRI in adults with CF (n = 12) of varying disease severities before and after different ACT to explore the obtainable information including mucus movement and static and dynamic airway ventilation.

Hypothesis

MRI is a novel and suitable tool for the assessment of lung structure and ventilation during ACT in adults with CF, which will provide a new outcome measure for use in future larger clinical trials in this area.

Each participant will complete three separate MRI scans, lasting approximately 20 minutes each, interspersed throughout the visit. They will also complete a 25 minute control period of resting breathing, and a 25 minute intervention period consisting of performing their usual ACT. The order of the intervention and control periods will be determined by randomisation. The ACT performed at each visit will be supervised by Jamie Wood and ACT will be performed according to International Physiotherapy Group for CF guidelines.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 103430 0
Mr Jamie Wood
Address 103430 0
Sir Charles Gairdner Hospital
Physiotherapy Department
Ground Floor A Block
Hospital Avenue Nedlands WA 6009
Country 103430 0
Australia
Phone 103430 0
+61 432 954 790
Fax 103430 0
Email 103430 0
[email protected]
Contact person for public queries
Name 103431 0
Mr Jamie Wood
Address 103431 0
Sir Charles Gairdner Hospital
Physiotherapy Department
Ground Floor A Block
Hospital Avenue Nedlands WA 6009
Country 103431 0
Australia
Phone 103431 0
+61 432 954 790
Fax 103431 0
Email 103431 0
[email protected]
Contact person for scientific queries
Name 103432 0
Mr Jamie Wood
Address 103432 0
Sir Charles Gairdner Hospital
Physiotherapy Department
Ground Floor A Block
Hospital Avenue Nedlands WA 6009
Country 103432 0
Australia
Phone 103432 0
+61 432 954 790
Fax 103432 0
Email 103432 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
The raw line data regarding the PRAGMA MRI scoring will be made available on request.
When will data be available (start and end dates)?
Unknown start date at present - following publication of the manuscript and until the proposed end of the HREC approval (31/12/2021)
Available to whom?
Available to those who request the information via contacting the principal investigator.
Available for what types of analyses?
Only to achieve the aims in the approved proposal and case-by-case at discretion of the Principal Investigator.
How or where can data be obtained?
Via the principal investigator ([email protected]) and following HREC approval at the site the research is being undertaken.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
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