Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000450617
Ethics application status
Approved
Date submitted
12/04/2023
Date registered
2/05/2023
Date last updated
21/05/2024
Date data sharing statement initially provided
2/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Discovering the effects of exercise on brain, spinal cord and muscle in people with Motor Neuron Disease (MND)
Scientific title
Using high-density surface electromyography to assess the neuroprotective potential of exercise in individuals with Motor Neuron Disease
Secondary ID [1] 309441 0
2021176
NHMRC Ideas Grant identification number
Universal Trial Number (UTN)
Trial acronym
ProtEx-MND
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Motor Neuron Disease 329693 0
Condition category
Condition code
Neurological 326592 326592 0 0
Neurodegenerative diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Arm 1: Moderate-intensity exercise training performed for 16 weeks, 3 times a week, 1 h per session. Each session will be fully supervised by exercise physiologists and PhD students, with a patient/therapist ratio of 1:1. The exercise training session will be individual and conducted face to face at the Victoria University Clinical Exercise and Rehabilitation (VUCER) clinic. Each session will be characterised by aerobic, resistance, balance and stretching exercises, distributed as follow:
- 20 min of cycling at a moderate intensity - 90% of the gas exchange threshold (the point where lactate starts to accumulate in the blood), evaluated during the incremental exercise test at exhaustion.
- 25 min of strength exercises at 70% of 1 Repetition Maximum (1RM). The first day of the exercise training program will be utilised to evaluate the 10 Repetitions Maximum (10RM), to assess the strength of the lower (leg extension and leg press exercises) and upper (chest press and biceps curl exercises) body muscle groups. 10RM is defined as the load that the subject is able to lift no more than 10 times. We will estimate the 1RM value from the measure of the 10RM, to avoid muscle damage during high-intensity exercise, such as the 1RM evaluation. Participants will perform one set of 10 repetitions of upper and lower body exercises on isotonic machines.
- 10 min of balance/proprioceptive exercises.
- 5 min of upper and lower extremity stretching exercises.

Adherence to the exercise training program will be assessed by the researchers involved in the project.
A maximum of 18 participants (the first 18 participants who opt-in to the additional byopsy component) will be asked to provide a skeletal muscle biopsy of the vastus lateralis muscle in the thigh, before and at the end of 16 weeks of intervention.
Intervention code [1] 325865 0
Treatment: Other
Intervention code [2] 325866 0
Rehabilitation
Comparator / control treatment
The control group will continue their usual daily activities and their standard of care. The standard of care consists of: Riluzole (the only treatment available for MND patients) twice/day, and visit to the MND multidisciplinary clinics (neurology, physiotherapy, occupational therapy, social work, psychology, speech pathology) once every 3 months.
Control group
Active

Outcomes
Primary outcome [1] 334444 0
Mean Motor Unit Action Potential (MUAP) discharge rate, evaluated with High-Density surface Electromyography (HDsEMG)
Timepoint [1] 334444 0
Baseline, 8 weeks, 16 weeks (primary timepoint), 24 weeks after intervention commencement
Primary outcome [2] 334445 0
Mean MUAP properties (i.e., Motor Unit Median Frequency, Root Mean Square, and Conduction Velocity), evaluated via HDsEMG. This will be assessed as a composite outcome.
Timepoint [2] 334445 0
Baseline, 8 weeks, 16 weeks (primary timepoint), 24 weeks after intervention commencement
Primary outcome [3] 334446 0
MUAP recruitment and de-recruitment threshold, evaluated by HDsEMG. This will be assessed as a composite outcome.
Timepoint [3] 334446 0
Baseline, 8 weeks, 16 weeks (primary timepoint), and 24 weeks after intervention commencement
Secondary outcome [1] 420684 0
Brain anatomy, measured with Magnetic Resonance Imaging (MRI)
Timepoint [1] 420684 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [2] 420685 0
White matter hyperintensity volume, measured via MRI
Timepoint [2] 420685 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [3] 420686 0
White matter structural changes, evaluated by MRI
Timepoint [3] 420686 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [4] 420687 0
Changes in cerebral metabolites relevant to neurodegeneration (i.e., N-acetylaspartate), via Magnetic Resonance Spectroscopy (MRS)
Timepoint [4] 420687 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [5] 420688 0
Skeletal muscle mitochondrial respiratory function via high-resolution respirometry
Timepoint [5] 420688 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [6] 420689 0
Skeletal muscle mitochondrial content via Transmission Electron Microscopy (TEM)
Timepoint [6] 420689 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [7] 420690 0
Skeletal muscle mitochondrial proteome, evaluated by mass-spectrometry-based proteomics
Timepoint [7] 420690 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [8] 420691 0
Skeletal muscle enzyme activities, evaluated by enzyme spectrophotometry
Timepoint [8] 420691 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [9] 420692 0
Autophagy flux, measured with Western Blot
Timepoint [9] 420692 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [10] 420693 0
Skeletal muscle mitochondrial super-complexes distribution, evaluated by Blue-Native Polyacrylamide Gel Electrophoresis
Timepoint [10] 420693 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [11] 420694 0
Maximal aerobic fitness, evaluated during an incremental exercise test at exhaustion
Timepoint [11] 420694 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [12] 420696 0
Maximal capacity of skeletal muscle oxygen extraction, evaluated via Near-Infrared Spectroscopy (NIRS)
Timepoint [12] 420696 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [13] 420699 0
Distance covered during a 6 min walking test
Timepoint [13] 420699 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [14] 420700 0
Muscle strength evaluated as one-repetition maximum (1RM) during biceps curl exercise
Timepoint [14] 420700 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [15] 420701 0
Lung function, evaluated during a spirometry test
Timepoint [15] 420701 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [16] 420702 0
Time to complete the "Timed Up and Go" test
Timepoint [16] 420702 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [17] 420703 0
Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R)
Timepoint [17] 420703 0
Baseline, 8 weeks, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [18] 420704 0
Disease progression rate, evaluated with the ALS disease progression score, which express the ALSFRS-R as a function of the disease duration (ALSFRS-R/symptoms duration in months)
Timepoint [18] 420704 0
Baseline, 8 weeks, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [19] 420705 0
Quality of Life (QoL), measured with the McGill QoL questionnaire
Timepoint [19] 420705 0
Baseline, 8 weeks, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [20] 420706 0
Fatigue, measured with the Fatigue Severity Scale (FSS)
Timepoint [20] 420706 0
Baseline, 8 weeks, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [21] 421007 0
Skeletal muscle mitochondrial membrane potential via high-resolution respirometry
Timepoint [21] 421007 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [22] 421008 0
Skeletal muscle mitochondrial morphology via Transmission Electron Microscopy (TEM)
Timepoint [22] 421008 0
Baseline and 16 weeks after intervention commencement
Secondary outcome [23] 421011 0
Muscle strength evaluated as one-repetition maximum (1RM) during leg extension exercise
Timepoint [23] 421011 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [24] 421012 0
Muscle strength evaluated as one-repetition maximum (1RM) during leg press exercise
Timepoint [24] 421012 0
Baseline, 16 weeks, and 24 weeks after intervention commencement
Secondary outcome [25] 421013 0
Muscle strength evaluated as one-repetition maximum (1RM) during vertical chest press exercise
Timepoint [25] 421013 0
Baseline, 16 weeks, and 24 weeks after intervention commencement

Eligibility
Key inclusion criteria
• Age: 18-80 y
• Diagnosis of definite or probable (laboratory-supported) MND
• Onset of MND less than or equal to 36 months before screening
• ALSFRS-R score greater than or equal to 24
• Forced Vital Capacity greater than or equal to 60 % of predicted
• Patients able to understand and comply with the requirements of the entire study
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Any medical disorder that would make physical activity contraindicated, including active malignancy, and severe heart, lung, renal, or liver failure
• Contraindications to have MRI (e.g., implanted metal, severe claustrophobia)
• Participation in pharmacological studies within the 30 days prior to screening

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

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
3/07/2023
Actual
30/01/2024
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
44
Accrual to date
2
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 313636 0
Government body
Name [1] 313636 0
National Health and Medical research council (NHMRC)
Country [1] 313636 0
Australia
Primary sponsor type
University
Name
Victoria University
Address
Ballarat Road
Footscray VIC 3011
Country
Australia
Secondary sponsor category [1] 315431 0
None
Name [1] 315431 0
None
Address [1] 315431 0
None
Country [1] 315431 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 312806 0
The Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 312806 0
Ethics committee country [1] 312806 0
Australia
Date submitted for ethics approval [1] 312806 0
25/04/2023
Approval date [1] 312806 0
28/09/2023
Ethics approval number [1] 312806 0
RMH92371

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

Contacts
Principal investigator
Name 125990 0
Dr Alessandra Ferri
Address 125990 0
Institute for Health and Sport
Victoria University
Ballarat Road
Footscray VIC 3011
Country 125990 0
Australia
Phone 125990 0
+61 3 9919 4756
Fax 125990 0
Email 125990 0
[email protected]
Contact person for public queries
Name 125991 0
Alessandra Ferri
Address 125991 0
Institute for Health and Sport
Victoria University
Ballarat Road
Footscray VIC 3011
Country 125991 0
Australia
Phone 125991 0
+61 3 9919 4756
Fax 125991 0
Email 125991 0
[email protected]
Contact person for scientific queries
Name 125992 0
Alessandra Ferri
Address 125992 0
Institute for Health and Sport
Victoria University
Ballarat Road
Footscray VIC 3011
Country 125992 0
Australia
Phone 125992 0
+61 3 9919 4756
Fax 125992 0
Email 125992 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?
All individual participant data collected during the trial, after de-identification
When will data be available (start and end dates)?
Data will be available following publications, no end date
Available to whom?
Researchers who provide a methodologically sound proposal
Available for what types of analyses?
IPD meta-analyses
How or where can data be obtained?
Access subject to approval by the Principal Investigator at [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.