Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12615000565549
Ethics application status
Approved
Date submitted
20/05/2015
Date registered
1/06/2015
Date last updated
8/02/2021
Date data sharing statement initially provided
8/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Lung Volume Recruitment in Neuromuscular Disease: Can ‘breath-stacking’ improve lung function, respiratory symptoms and quality of life for people with neuromuscular disease?
Scientific title
The effect of lung volume recruitment, performed daily for three months, on maximal insufflation capacity in people with neuromuscular disease and respiratory system involvement.
Secondary ID [1] 286760 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Neuromuscular disease
 295130 0
Motor neurone disease 295131 0
Muscular dystrophy 295132 0
Spinal cord injury 295133 0
Condition category
Condition code
Neurological 295377 295377 0 0
Neurodegenerative diseases
Physical Medicine / Rehabilitation 295378 295378 0 0
Physiotherapy
Respiratory 295442 295442 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment group 1: Breath-stacking breathing exercises performed at least twice daily, for 3 months

- A routine of deep breaths, augmented using a manual resuscitation bag attached to a mouthpiece or face mask (“MIC breath”), followed by normal breaths is prescribed. The prescription will be tailored to the individual participant, with a treatment aim of 3-5 MIC breaths repeated 3-5 times.

Participants will be reviewed by an experienced respiratory physiotherapist who will trial and tailor the breath-stacking routine, then educate and provide instructions for the participant during an individual session of approximately 20 minutes duration at baseline / Visit 1.

Adherence will be monitored in both the Intervention group (Treatment group 1) and Active Control (Treatment group 2) using a Participant Diary. Additionally, a data logger attached to the manual resuscitation bag will confirm adherence in Treatment group 1.
Intervention code [1] 291915 0
Rehabilitation
Intervention code [2] 291916 0
Treatment: Devices
Comparator / control treatment
Treatment group 2: Diaphragmatic breathing exercises performed at least twice daily, for 3 months

- A routine of deep breaths, focusing on the diaphragm to produce the movement, followed by normal breaths is prescribed. The prescription will be tailored to the individual participant, with the treatment aim of performing this cycle for 10 minutes.

Participants will be reviewed by an experienced respiratory physiotherapist who will trial and tailor the diaphragmatic breathing exercise routine, then educate and provide instructions for the participant during an individual session of approximately 20 minutes duration at baseline / Visit 1.
Control group
Active

Outcomes
Primary outcome [1] 295112 0
Maximal Insufflation Capacity (MIC), defined as exhaled volume immediately following a lung volume recruitment manoeuvre (breath-stacking) to maximum insufflation capacity.

Measured using a spirometer and/or pneumotach connected to a face mask or mouthpiece, in the sitting position.
Timepoint [1] 295112 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [1] 314792 0
Forced Vital Capacity (FVC), measured using a spirometer and/or pneumotach connected to a face mask or mouthpiece, in the sitting position.
Timepoint [1] 314792 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [2] 314793 0
MIC minus FVC difference.

This value is calculated from Primary Outcome 1 (MIC) and Secondary Outcome 1 (FVC), based on the best value out of three attempts obtained for MIC and FVC.
Timepoint [2] 314793 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [3] 314794 0
Lung volume, particularly total lung capacity (TLC), obtained using the multiple-breath nitrogen washout technique, measured using a portable pulmonary function test system in the sitting position.
Timepoint [3] 314794 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [4] 314795 0
Total respiratory system compliance (Crs), derived from pressure and volume measurements obtained non-invasively using a pneumotach and face mask or mouthpiece, during a sub-maximal insufflation manoeuvre, performed in the sitting position.
Timepoint [4] 314795 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [5] 314796 0
Unassisted Peak Cough Flow (PCFunAx), measured using a peak flow meter and/or pneumotach connected to an oronasal mask as the participant performs an unassisted, spontaneous cough in the sitting position
Timepoint [5] 314796 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [6] 314797 0
Assisted Peak Cough Flow (PCFAx), measured using a peak flow meter and/or pneumotach connected to an oronasal mask as the participant performs a cough immediately following a breath-stacking manoeuvre, in the sitting position
Timepoint [6] 314797 0
Baseline and at 1, 2 and 3 months after intervention commencement
Secondary outcome [7] 314798 0
Respiratory muscle performance, evaluated using maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP) and sniff nasal inspiratory pressure (SNIP).

MIP will be measured at residual volume (RV), whilst MEP will be measured at total lung capacity (TLC). MIP, MEP and SNIP will all be measured in the sitting position and according to standardised guidelines published by the ATS/ERS 2002, using a portable pulmonary function testing system equipped to measure pressure.
Timepoint [7] 314798 0
Baseline and at 3 months after intervention commencement
Secondary outcome [8] 314799 0
Health related quality of life, as assessed using the Assessment of Quality of Life questionnaire (AQoL-8D) and the Severe Respiratory Insufficiency questionnaire (SRI)
Timepoint [8] 314799 0
Baseline and at 3 months after intervention commencement
Secondary outcome [9] 314800 0
Adherence to therapy, as assessed using Participant Diary

Timepoint [9] 314800 0
1, 2 and 3 months after intervention commencement
Secondary outcome [10] 314801 0
Adherence to lung volume recruitment (Treatment group 1), as assessed using data logger attached to the manual resuscitation bag
Timepoint [10] 314801 0
1, 2 and 3 months after intervention commencement
Secondary outcome [11] 314802 0
Side-effects and adverse events, as assessed by participant self-report.

Potential side-effects associated with taking repeated deep breaths include discomfort or musculoskeletal soreness of the chest wall, and light-headedness and/or transient fall in blood pressure.

Theoretically, pneumothoraces can occur at very high inspiratory pressures and would constitute an adverse event.
Timepoint [11] 314802 0
1, 2 and 3 months after intervention commencement
Secondary outcome [12] 314803 0
Hospitalisation rate, as assessed by participant self-report
Timepoint [12] 314803 0
1, 2 and 3 months after intervention commencement

Eligibility
Key inclusion criteria
Neuromuscular disease of >3 months duration
Respiratory system involvement (FVC <80% predicted)
Minimum age
14 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Previously prescribed daily LVR therapy which was performed for a period of >3 consecutive months in the last 12 months, or >6 consecutive weeks within the past 6 months
Medical instability
Inpatient admission for acute respiratory compromise in the preceding 6 weeks
Inability to provide informed consent
Not proficient in English
Requiring invasive ventilation via tracheostomy tube
Previous history or perceived risk factors for pneumothorax
Contraindication or precautions for positive pressure therapy / LVR manoeuvres

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)
Participants will be enrolled if they meet the eligibility criteria and consent to participate.
Following baseline data collection, participants will undergo a short trial of lung volume recruitment, with re-assessment of lung function. If participants demonstrate a response to LVR during this short-term trial, defined by improvement in MIC-VC difference of greater than or equal to 10% of VC, they shall proceed to study randomisation.
Participants will be stratified according to disease classification and randomly block-allocated to either the Active Control or Intervention group by sealed opaque envelope method
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be stratified according to disease classification.
Randomisation will occur in blocks.
Random order generation will occur using simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
N/A
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Sample size calculations are based on published data regarding the change in the primary outcome, MIC, following three-months of regular lung volume recruitment (Kaminska 2015).

To detect a mean treatment difference of 150ml in MIC over three months with a standard deviation of 310ml, assuming 80% power and statistical significance level of 0.05, this research study requires 36 participants per group. We will recruit a total number of 83 participants to allow for a 15% drop-out rate.

Linear models will be used to assess between group differences in the primary and secondary outcomes.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
30/08/2015
Actual
2/09/2015
Date of last participant enrolment
Anticipated
Actual
21/05/2019
Date of last data collection
Anticipated
Actual
20/08/2019
Sample size
Target
80
Accrual to date
Final
80
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 3810 0
Austin Health - Heidelberg Repatriation Hospital - Heidelberg West
Recruitment hospital [2] 3811 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [3] 3812 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 9695 0
3084 - Heidelberg
Recruitment postcode(s) [2] 9696 0
3162 - Caulfield
Recruitment postcode(s) [3] 9697 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 291303 0
Government body
Name [1] 291303 0
NHMRC: National Health and Medical Research Council
Country [1] 291303 0
Australia
Funding source category [2] 291304 0
Charities/Societies/Foundations
Name [2] 291304 0
Institute for Breathing and Sleep
Country [2] 291304 0
Australia
Funding source category [3] 291305 0
Charities/Societies/Foundations
Name [3] 291305 0
Physiotherapy Research Foundation
Country [3] 291305 0
Australia
Funding source category [4] 291306 0
Hospital
Name [4] 291306 0
Austin Health
Country [4] 291306 0
Australia
Funding source category [5] 307805 0
Charities/Societies/Foundations
Name [5] 307805 0
Motor Neurone Disease Research Institute of Australia
Country [5] 307805 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Institute for Breathing and Sleep
Address
Bowen Centre, Austin Hospital
145 Studley Road,
Heidelberg Vic 3084
Country
Australia
Secondary sponsor category [1] 289986 0
Hospital
Name [1] 289986 0
Austin Health
Address [1] 289986 0
145 Studley Road,
Heidelberg Vic 3084
Country [1] 289986 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292870 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 292870 0
Ethics committee country [1] 292870 0
Australia
Date submitted for ethics approval [1] 292870 0
23/04/2015
Approval date [1] 292870 0
01/06/2015
Ethics approval number [1] 292870 0
HREC/15/Austin/117
Ethics committee name [2] 292871 0
Calvary Health Care Bethlehem Research Ethics and Ethics Committee
Ethics committee address [2] 292871 0
Ethics committee country [2] 292871 0
Australia
Date submitted for ethics approval [2] 292871 0
28/05/2015
Approval date [2] 292871 0
18/06/2015
Ethics approval number [2] 292871 0
HREC/15/Austin/117
Ethics committee name [3] 298297 0
The Royal Children's Hospital Melbourne
Ethics committee address [3] 298297 0
Ethics committee country [3] 298297 0
Australia
Date submitted for ethics approval [3] 298297 0
13/09/2016
Approval date [3] 298297 0
28/11/2016
Ethics approval number [3] 298297 0
RCH HREC Reference Number 36150A

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57446 0
Dr David Berlowitz
Address 57446 0
Austin Health
145 Studley Road
Heidelberg Vic 3084
Country 57446 0
Australia
Phone 57446 0
+61 3 9496 3871
Fax 57446 0
+ 61 3 9496 5124
Email 57446 0
[email protected]
Contact person for public queries
Name 57447 0
Nicole Sheers
Address 57447 0
Austin Health
145 Studley Road
Heidelberg Vic 3084
Country 57447 0
Australia
Phone 57447 0
61 3 9496 3877
Fax 57447 0
+ 61 3 9496 5768
Email 57447 0
[email protected]
Contact person for scientific queries
Name 57448 0
David Berlowitz
Address 57448 0
Austin Health
145 Studley Road
Heidelberg Vic 3084
Country 57448 0
Australia
Phone 57448 0
+61 3 9496 3871
Fax 57448 0
+ 61 3 9496 5124
Email 57448 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
At this stage the Principal Investigators have not discussed sharing of trial data and whether the Ethics Application submitted and approved in 2015 or Informed Consent obtained would allow this to occur.


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
SourceTitleYear of PublicationDOI
EmbaseRapidly and slowly progressive neuromuscular disease: Differences in pulmonary function, respiratory tract infections and response to lung volume recruitment therapy (LVR).2022https://dx.doi.org/10.1136/bmjresp-2022-001241
Dimensions AIA Randomized Controlled Clinical Trial of Lung Volume Recruitment in Adults with Neuromuscular Disease2023https://doi.org/10.1513/annalsats.202212-1062oc
N.B. These documents automatically identified may not have been verified by the study sponsor.