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Trial registered on ANZCTR


Registration number
ACTRN12618001837213
Ethics application status
Approved
Date submitted
22/10/2018
Date registered
12/11/2018
Date last updated
23/04/2021
Date data sharing statement initially provided
12/11/2018
Type of registration
Retrospectively registered

Titles & IDs
Public title
Breathing Muscle Training in Parkinson's Disease
Scientific title
Improvement of pulmonary function, gait and mobility in Parkinson’s Disease following Inspiratory Muscle Training
Secondary ID [1] 293891 0
None
Universal Trial Number (UTN)
U1111-1208-6346
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Parkinson's Disease 306361 0
Condition category
Condition code
Neurological 305446 305446 0 0
Parkinson's disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Inspiratory Muscle Training (IMT)

Inspiratory muscle training is achieved by using a POWERbreathe RMT/IMT Class 1 Medical Device (www.powerbreathe.com). They are advanced pressure threshold loading devices that strengthen inspiratory muscles by creating a resistance against the in-breath and are clinically proven to be beneficial for COPD, asthma and heart failure. They are hand held devices that can be used at home after initial training.

Interval-Based Training
All participants will undergo an 8 week home based H-IMT or S-IMT program after initial training by a senior physiotherapist with expertise in the use of the IMT devise. The home IMT resistive exercise intervention is based on the previously published protocols of Hill et al. (2010). IMT adherence will be recorded by the participants in their exercise logs. At week 2 participants will be reviewed in the clinic to ensure that they are performing the IMT optimally and to increase training loads. Subsequently, there will be weekly phone contact and the training load increased according to patient feedback.

The IMT program is based on a protocol previously demonstrated to be feasible and effective (Hill et al. 2010). Initial training will be one on one, face to face and demonstrated and guided by a trained physiotherapist. It will take about 1 hour. Training takes place with the patient seated, wearing a nose clip. Patients are permitted to lean forward and fix their upper limbs on the arms of chair or table if desired. Training commences with a 1-minute warm-up at 50% of the target inspiratory training load (see “Training loads”). Thereafter, an interval based training approach is used, characterized by a work to rest ratio of 2 minutes (work) to 1 minute (rest). This 3-minute cycle is repeated 7 times, resulting in a 21-minute training session (ie, 14 minutes of loaded breathing). Patients are permitted to select their own breathing pattern, and expiration is unloaded.

Subsequent training is undertaken at home 3 times a week for 8 weeks, and patients are encouraged to record their training sessions in an exercise diary. At week 2 there is a second one on one, face to face training session with the physiotherapist to ensure that the correct techniques are used, and to demonstrate how to increase training loads. Once weekly phone calls will be made on weeks 3-8 to answer any questions regarding the home training.

Training Loads
For the initial 2-minute interval, a training load is selected equivalent to 30% of a patient’s PImax. Loads less than 30% of PImax are insufficient to induce improvement in inspiratory muscle strength. Consistent with the current recommendations for whole-body exercise training, we will use a symptom limited approach to guide the progression of training loads. We select loads that patients describe as somewhat hard—that is, between 12 and 14 on the Rating of Perceived Exertion (RPE) scale. Training loads are increased during the designated rest intervals to achieve these RPE targets. Patients train at loads corresponding to a higher RPE if tolerated and there are no abnormal symptoms (eg, prolonged delayed onset muscle soreness).

On completion of the first training session, patients are often training at loads equal to approximately 40% of PImax. The inspiratory load can usually be increased rapidly during the first 4 weeks of training, mainly due to neurosensory adaptation reflecting desensitization to the inspiratory loads and improved recruitment of motor units. Thereafter, the rate of increase often slows, and further increases in muscle function are likely to result from muscular hypertrophy.

Sham inspiratory muscle training (S-IMT) will be performed at 10% of PImax with a 2-3 % increase in training load every week (Hill et al. 2006, 2010).

Reassessment and maintenance
Reassessment of all outcome measures is performed at completion of the training and 6 months after the initiation of training. Training-related gains are lost within 12 months if regular IMT is ceased. In order to optimize the maintenance of benefits, we encourage the completion of at least 2 IMT sessions each week at the load achieved during the final session of the 8-week program. At 6 months, those patients in the sham group will be offered H-IMT for 8 weeks, followed by reassessment after completion of training and at 6 months.
Intervention code [1] 300160 0
Rehabilitation
Comparator / control treatment
A prospective, double-blind, randomised, controlled design will be used with a treatment group undergoing 8 weeks of high intensity Inspiratory Muscle Training (H-IMT) and a control group undergoing 8 weeks of sham IMT (S-IMT).
Control group
Placebo

Outcomes
Primary outcome [1] 304592 0
Peak inspiratory pressure (PImax) – (maximal static mouth pressures during inspiration)
Spirometry - The apparatus consists of a well fitting mouthpiece connected to a small chamber, to which a pressure gauge is connected. A small leak in the chamber prevents the patient from using buccal muscles to generate the pressure. For MIP the patient stops breathing at a set volume, usually residual volume, and tries to sustain a maximal negative pressure, usually for one second or more.
Timepoint [1] 304592 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [1] 342469 0
Forced Expiratory Volume 1s (Spirometry)
Timepoint [1] 342469 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [2] 342470 0
Forced Vital capacity (FVC) (Spirometry)
Timepoint [2] 342470 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [3] 353175 0
Peak inspiratory Flow (Spirometry)
Timepoint [3] 353175 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [4] 353696 0
Peak Expiratory Flow (Spirometry)
Timepoint [4] 353696 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [5] 353697 0
Functional Residual Capacity (FRC) (plethysmography),
Timepoint [5] 353697 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [6] 353698 0
Total Lung Capacity (plethysmography),
Timepoint [6] 353698 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [7] 353699 0
Residual Volume (plethysmography)
Timepoint [7] 353699 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [8] 353700 0
Inspiratory capacity (plethysmography)
Timepoint [8] 353700 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [9] 353701 0
Peak expiratory pressures (Maximal Static mouth pressures during expiration) (Spirometry)
Timepoint [9] 353701 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [10] 353702 0
Maximal Voluntary Ventilation (Spirometry)
Timepoint [10] 353702 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [11] 353703 0
Timed Up and Go Test
Timepoint [11] 353703 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [12] 353704 0
10m Walk Test
Timepoint [12] 353704 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [13] 353705 0
Berg Balance Test
Timepoint [13] 353705 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [14] 353706 0
Dynamic Gait Index
Timepoint [14] 353706 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [15] 353707 0
Balance master (Motor Adaptation Test)
Timepoint [15] 353707 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [16] 353708 0
Functional Reach Test
Timepoint [16] 353708 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [17] 353709 0
Activities-specific Balance Confidence (ABC)
Timepoint [17] 353709 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [18] 353710 0
Dizziness Handicap Inventory (DHI),
Timepoint [18] 353710 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [19] 353711 0
Self reporting falls questionnaire
Based on:
Talbot, L. A., Musiol, R. J., et al. (2005). "Falls in young, middle-aged and older community dwelling adults: perceived cause, environmental factors and injury." BMC Public Health 5(1): 86.
Timepoint [19] 353711 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [20] 353712 0
PDQ-39
Timepoint [20] 353712 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [21] 353713 0
Fatigue severity scale (FSS)
Timepoint [21] 353713 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [22] 353715 0
Self-reported dysphagia measure will be recorded using the EAT-10 questionnaire
Timepoint [22] 353715 0
9 weeks (1 week after completion of 8 weeks of training)
Secondary outcome [23] 353716 0
Acoustic speech protocol
Measures will include:
- Sustained vowel /a/ phonation: patient will be instructed to say ‘ah’ for as long as they can. Length of phonation will be measured with a stop watch.
- Maximum phonation value: (recorded value of 3 attempts). Patient will be instructed to say ‘ah’ for as loud and as long as they can. dBSPL will be measured using a calibrated sound pressure level metre.
- Average reading of dBSPL (Rainbow passage) and average conversation dBSPL in a 2 minute conversation using a calibrated sound pressure level meter.
- s:z ratio: this is an indicator of laryngeal pathology. The participant will be instructed to:
o take a deep breath and then to sustain the sound ‘s’ followed by ‘z’ for as long as possible at a comfortable pitch and loudness on one exhalation, without straining. Using a stopwatch, time (in seconds) the clinician will record how long the participant can sustain the sound. Participant will repeat this process x3
o S:Z Ratio will be calculated by dividing the time of the longest duration ‘s’ by the time of the longest duration ‘z’

- Assessment of Intelligibility of Dysarthric Speech (AIDS) 20mins.
This is a tool for quantifying single-word intelligibility, sentence intelligibility, and speaking rate of adult and adolescent speakers with dysarthria. Standard protocols containing speaker tasks, recording techniques, and listener response formats are employed in order to obtain a variety of intelligibility and communication efficiency measures
Timepoint [23] 353716 0
9 weeks (1 week after completion of 8 weeks of training)

Eligibility
Key inclusion criteria
1. Mild to moderate Idiopathic Parkinson’s Disease (Hoehn and Yahr stage 1-3).
2. Normal age matched subjects with no significant medical conditions.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
PD subjects
1. Moderate to severe cognitive or psychiatric dysfunction
2. Significant cardiopulmonary disease
3. Other medical or neurological comorbidities that would preclude testing for mobility and balance (e.g. stroke, severe arthritis etc.)
4. IMT necessitates the generation of large negative intrathoracic pressures; therefore, people who are at risk of spontaneous pneumothorax or rib fractures will be excluded from participation.

Exclusion criteria for normal age matched subjects:
1. IMT necessitates the generation of large negative intrathoracic pressures; therefore, people who are at risk of spontaneous pneumothorax or rib fractures will be excluded from participation

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)
Neurologist assessing for inclusion in trial will be blinded to subsequent allocation to real or sham tDCS. Holder of allocation schedule will not be involved in assessment for inclusion.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Block randomization using computer sequence generation
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The results from the 2 groups of participants (PD and non-PD) will be analysed separately. Descriptive analysis will include means, standard deviations, and group characteristics at baseline. The effects of intervention (H-IMT) will be evaluated in PD participants by comparison of primary and secondary outcomes before and after IMT at 8 weeks and 6 months. Comparisons of categorical variables will be made using chi-square tests. Continuous measures or scales will be compared using ANOVA. Data will be checked for normality using the Shapiro-Wilk test. Corrections will be made for multiple testing. A similar analysis will be performed on data from the non-PD participants.
In addition, a comparison of pulmonary function in PD participants and age matched normal participants will be made using t-tests, corrected for multiple comparisons.
Sample size calculation
We aim to enrol ~30 patients and 30 normal subjects for the study (with an expected maximum drop out of ~20%). The mean PImax score in the PD is estimated to be 58.6 cm H20 (standard deviation of 12.3, Loana et al. 2012). The treatment effect has been found to vary between 28 and 34% increase in patients with COPD and MS (Hill et al. 2006; Ray et al. 2013). We would detect a 25% increase in PImax with intervention at a two-sided significance level of 0.05, with a power of 80% if we enrol 22 patients in the present study.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
22/10/2018
Date of last participant enrolment
Anticipated
31/10/2022
Actual
Date of last data collection
Anticipated
28/04/2023
Actual
Sample size
Target
60
Accrual to date
12
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 12233 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment postcode(s) [1] 24419 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 298514 0
Other
Name [1] 298514 0
Perron Institute for Neurological and Translational Science
Country [1] 298514 0
Australia
Funding source category [2] 308436 0
Charities/Societies/Foundations
Name [2] 308436 0
Parkinson's Western Australia
Country [2] 308436 0
Australia
Primary sponsor type
Individual
Name
Clinical Professor Soumya Ghosh
Address
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 297661 0
None
Name [1] 297661 0
Address [1] 297661 0
Country [1] 297661 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299492 0
Bellberry Human Research Ethics Committee Committee C (TGA HREC Code: EC00430)
Ethics committee address [1] 299492 0
Ethics committee country [1] 299492 0
Australia
Date submitted for ethics approval [1] 299492 0
18/06/2018
Approval date [1] 299492 0
14/08/2018
Ethics approval number [1] 299492 0
2018-06-447-A-1

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

Contacts
Principal investigator
Name 80598 0
Prof Soumya Ghosh
Address 80598 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 80598 0
Australia
Phone 80598 0
+61864570200
Fax 80598 0
+61 8 64570281
Email 80598 0
Soumya.Ghosh@health.wa.gov.au
Contact person for public queries
Name 80599 0
Jesse Dixon
Address 80599 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 80599 0
Australia
Phone 80599 0
+61864570207
Fax 80599 0
+61 8 64570281
Email 80599 0
Jesse.Dixon@health.wa.gov.au
Contact person for scientific queries
Name 80600 0
Soumya Ghosh
Address 80600 0
Perron Institute for Neurological and Translational Science
QEII Medical Centre RR Block
Verdun Street, Nedlands WA 6009
Country 80600 0
Australia
Phone 80600 0
+61864570200
Fax 80600 0
+61 8 64570281
Email 80600 0
Soumya.Ghosh@health.wa.gov.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Lack of funding


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.