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Trial registered on ANZCTR


Registration number
ACTRN12624001405505
Ethics application status
Approved
Date submitted
11/11/2024
Date registered
28/11/2024
Date last updated
28/11/2024
Date data sharing statement initially provided
28/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Combined Hyperinflation and Expiratory Strength Training in People Living With Motor Neurone Disease (CHEST-MND: PRO)
Scientific title
Prospective Controlled Run-in Study Evaluating Combined Respiratory Training on Cough and Respiratory Function in people living with Motor Neurone Disease
Secondary ID [1] 313232 0
Nil known
Universal Trial Number (UTN)
U1111-1314-8223
Trial acronym
CHEST-MND: PRO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor neurone disease 335577 0
Condition category
Condition code
Respiratory 332149 332149 0 0
Other respiratory disorders / diseases
Neurological 332150 332150 0 0
Neurodegenerative diseases
Physical Medicine / Rehabilitation 332169 332169 0 0
Physiotherapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
All enrolled participants will commence a combined lung volume recruitment and expiratory muscle strength training exercise regimen (LVR and EMST), following a 5-week no-intervention lead-in period.

Intervention description: LVR uses a self-inflating bag (similar to a resuscitation bag) with a mouthpiece or mask to deliver consecutive insufflations (i.e., large “puffs” of air), to “stack” a larger volume of air than can be inspired spontaneously.
EMST uses a spring-loaded pressure threshold device to provide resistance as one breaths out.
This study combines these two devices, so that a person "stacks" a volume of air in using the LVR bag, and then exhales through the resistive training device.

Intervention dose: Participants will be instructed to complete 5 sets of 5 repetitions of combined LVR+EMST into a single device on 5 days per week for 5 weeks (total of 25 intervention sessions over a 5-week period). One repetition consists of an individually prescribed number of compressions via the LVR bag to reach the maximal tolerated inflation capacity, followed by a forceful expiration through the EMST device, set at 50% of the participant’s maximal expiratory pressure (MEP). Exercises are usually performed seated (chair or wheelchair), and take approximately 20 minutes to complete.

An experienced health care professional (e.g. physiotherapist with experience in the provision of respiratory care) will prescribe the therapy and ensure participants are trained in its appropriate use. This initial training will be performed in the participant's home, face-to-face.
Subsequent sessions will be conducted by the participant themselves, with the assistance of their caregiver (if required), in their home environment. Training technique will be reviewed by a member of the research team via telehealth weekly for the duration of the study.

Adherence to the intervention will be assessed via a participant diary, as well as via a LVR counter attached to the LVR kit.
Intervention code [1] 329837 0
Rehabilitation
Comparator / control treatment
This study is a prospective controlled run-in trial.
Participants will undertake a 5-week no treatment period (dose of treatment = nil)
Control group
Active

Outcomes
Primary outcome [1] 339737 0
Peak cough flow
Timepoint [1] 339737 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Also measured weekly via telehealth (Weeks 1-4 and Weeks 6-9).
Secondary outcome [1] 441043 0
Forced vital capacity
Timepoint [1] 441043 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [2] 441044 0
Lung insufflation capacity
Timepoint [2] 441044 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [3] 441045 0
Cough spirometry
Timepoint [3] 441045 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [4] 441046 0
Maximum phonation time
Timepoint [4] 441046 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Also measured weekly via telehealth (Weeks 1-4 and Weeks 6-9).
Secondary outcome [5] 441047 0
Maximal inspiratory pressure
Timepoint [5] 441047 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [6] 441048 0
Maximal expiratory pressure
Timepoint [6] 441048 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [7] 441049 0
Sniff nasal inspiratory pressure
Timepoint [7] 441049 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [8] 441050 0
Global rating of change: cough effectiveness
Timepoint [8] 441050 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Also measured weekly via telehealth (Weeks 1-4 and Weeks 6-9).
Secondary outcome [9] 441051 0
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Timepoint [9] 441051 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [10] 441052 0
Bulbar function, assessed as a composite measure
Timepoint [10] 441052 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [11] 441053 0
International Dysphagia Diet Standardisation Initiative Functional Diet Scale (IDDSI-FDS)
Timepoint [11] 441053 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [12] 441054 0
Dyspnea
Timepoint [12] 441054 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [13] 441055 0
Severe Respiratory Insufficiency Questionnaire (SRI)
Timepoint [13] 441055 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [14] 441056 0
Care giver burden, assessed as a composite outcome
Timepoint [14] 441056 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [15] 441057 0
Exercise therapy burden, assessed as a composite outcome
Timepoint [15] 441057 0
Post LVR+EMST (Week 10).
Secondary outcome [16] 441058 0
Adherence to LVR+EMST
Timepoint [16] 441058 0
Post LVR+EMST (Week 10).
Secondary outcome [17] 441059 0
Side effects and adverse events during LVR+EMST
Timepoint [17] 441059 0
Assessed weekly (question posed to participant) at Weeks 1-4 (via telehealth), Weeks 6-9 (via telehealth) and in-person Post LVR+EMST (Week 10). Events will be collated and reported per participant for the study period.
Secondary outcome [18] 441060 0
Healthcare utilisation
Timepoint [18] 441060 0
Post LVR+EMST (Week 10).
Secondary outcome [19] 441061 0
Participant qualitative experience of intervention
Timepoint [19] 441061 0
Post LVR+EMST (Week 10).
Secondary outcome [20] 441964 0
Bulbar function - speech symptoms
Timepoint [20] 441964 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [21] 441965 0
Bulbar function - swallowing symptoms
Timepoint [21] 441965 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).
Secondary outcome [22] 441966 0
Bulbar function - salivation symptoms
Timepoint [22] 441966 0
Measured at Baseline 1 (Week 0), Baseline 2 (Week 5), and Post LVR+EMST (Week 10).

Eligibility
Key inclusion criteria
A diagnosis of MND/ALS, according to the revised El Escorial criteria (possible, probable laboratory supported, probable, or definite).
Forced vital capacity (FVC) greater than or equal to 50% predicted normal reference values.
Naïve to lung volume recruitment (LVR) and expiratory muscle strength training (EMST).
Provided a signed and dated informed consent form (or witnessed signed form if unable to write),
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Medical instability (e.g., acute medical issues/hospitalisation).
History of stroke, head and neck cancer or other concomitant disorder that might contribute to dysphagia or respiratory impairment.
Diagnosis of frontotemporal dementia or advanced cognitive impairment.
Use of prescription mechanical insufflation-exsufflation or non-invasive ventilation devices.
Tracheostomy / use of invasive mechanical ventilation.
Enrolment in another research investigation that might impact cough or respiratory function.
Contraindications for respiratory training (i.e., history of pneumothorax, severe chronic obstructive pulmonary disease).
Unable to physically perform or can’t tolerate LVR.
Home visit safety risk.
Unable to provide informed consent.
Limited English proficiency.
Resides more than 2 hours travel time from Austin Health.

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
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study is a pilot and feasibility study and as such is not powered to detect a difference in the primary outcome. To adequately evaluate feasibility and acceptability, 16 participants with MND will be sought for this study. This sample size exceeds the minimum recommended to achieve saturation for qualitative research of this nature (10-13 participants),(Francis et al 2010) and the “12 participant rule of thumb” for pilot studies.(Julious 2005) Moreover, it is feasible based on conservative estimates of diagnosis, with approximately two people diagnosed with MND per day in Australia, with an estimated 10 people/month residing in Victoria. It is anticipated approximately 2 participants will be recruited per month during the 12-month available for enrolment.

Consultation with a biostatistician will be undertaken through the University of Melbourne. The results of the study will be analysed in accordance with the intention to treat principle using linear models. Change over time for the period Baseline 1 to Baseline 2 will be compared to the period Baseline 2 to Post LVR+EMST. Quantitative data analysis will be undertaken using STATA and/or R software. Qualitative data will be primarily deductive. Data will be coded into 8 domains of the TFA and 6 domains of the COM-B. Sub-themes within these domains will be identified. Any themes that do not naturally fit within the TFA or COM-B will be inductively identified and included. A proportion of the interviews will be double-coded to ensure consistency.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/12/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
16
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27287 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 27288 0
Calvary Health Care Bethlehem Ltd - Caulfield
Recruitment hospital [3] 27289 0
The Northern Hospital - Epping
Recruitment postcode(s) [1] 43374 0
3084 - Heidelberg
Recruitment postcode(s) [2] 43375 0
3162 - Caulfield
Recruitment postcode(s) [3] 43405 0
3076 - Epping

Funding & Sponsors
Funding source category [1] 317674 0
Charities/Societies/Foundations
Name [1] 317674 0
FightMND
Country [1] 317674 0
Australia
Primary sponsor type
Other Collaborative groups
Name
Institute for Breathing and Sleep (IBAS)
Address
Country
Australia
Secondary sponsor category [1] 319992 0
None
Name [1] 319992 0
Address [1] 319992 0
Country [1] 319992 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316373 0
Austin Health Human Research Ethics Committee
Ethics committee address [1] 316373 0
https://www.austin.org.au/Office-for-Research/
Ethics committee country [1] 316373 0
Australia
Date submitted for ethics approval [1] 316373 0
15/07/2024
Approval date [1] 316373 0
02/10/2024
Ethics approval number [1] 316373 0
HREC/110306/Austin-2024

Summary
Brief summary
Breathing and coughing difficulties are extremely distressing for people living with MND and therapies that improve breathing capacity and related symptoms are needed. Our research team has previously shown that breathing exercises using a hand-held device to help people take a bigger breath (lung volume recruitment) can produce important changes in lung capacity. Separately, our collaborators in the United States have found that exercises using a different hand-held device (expiratory muscle strength training) can improve expiratory muscle strength in people with MND. This research project will evaluate whether combining these two therapies together has added benefit. We will test whether five weeks of combined respiratory training is feasible and acceptable to people living with MND and their carers, and whether it improves breathing and cough strength, symptoms and quality of life in people affected by MND.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 137690 0
Dr Nicole Sheers
Address 137690 0
Institute for Breathing and Sleep; Level 5, Harold Stokes Building; Austin Hospital, 145 Studley Road; Heidelberg, VIC, 3084
Country 137690 0
Australia
Phone 137690 0
+61 468 862 693
Fax 137690 0
Email 137690 0
[email protected]
Contact person for public queries
Name 137691 0
Nicole Sheers
Address 137691 0
Institute for Breathing and Sleep; Level 5, Harold Stokes Building; Austin Hospital, 145 Studley Road; Heidelberg, VIC, 3084
Country 137691 0
Australia
Phone 137691 0
+61 468 862 693
Fax 137691 0
Email 137691 0
[email protected]
Contact person for scientific queries
Name 137692 0
Nicole Sheers
Address 137692 0
Institute for Breathing and Sleep; Level 5, Harold Stokes Building; Austin Hospital, 145 Studley Road; Heidelberg, VIC, 3084
Country 137692 0
Australia
Phone 137692 0
+61 468 862 693
Fax 137692 0
Email 137692 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?
This research trial has an a priori plan to conduct an individual patient data meta-analysis with data from a similar pilot study currently underway in Florida, USA (Principal Investigator Lauren Tabor Gray: ClinicalTrials.gov Identifier: NCT05913882). Additionally, de-identified data will be made available to selected Australian and international researchers upon approval of written requests.
When will data be available (start and end dates)?
Start date: Immediately following publication
End date: No end date determined
Available to whom?
Principal Investigator Lauren Tabor Gray: ClinicalTrials.gov Identifier: NCT05913882.
Additionally, investigators whose proposed use of the individual participant data has been approved by an independent review committee will be eligible to request individual participant data. Data requesters will need to sign a data access agreement.
Available for what types of analyses?
For IPD meta-analysis and de-identified individual data.
How or where can data be obtained?
Proposals to analyse individual participant data should be directed to the principal investigator, Dr Nicole Sheers (via email to: [email protected])


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
No additional documents have been identified.