Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617001244392
Ethics application status
Approved
Date submitted
22/08/2017
Date registered
25/08/2017
Date last updated
21/05/2024
Date data sharing statement initially provided
2/05/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effects of Exercise Training on Muscle Strength and Aerobic Capacity in Patients with Amyotrophic Lateral Sclerosis
Scientific title
Tailored Exercise Training as a New Intervention to Counteract Muscle Disuse in Patients with Amyotrophic Lateral Sclerosis: Effects on Muscle Strength and Aerobic Capacity
Secondary ID [1] 292704 0
ID from funding body (Perpetual Philanthropy): IPAP2017/1191
Universal Trial Number (UTN)
Trial acronym
TRAIN-ALS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Amyotrophic Lateral Sclerosis 304460 0
Condition category
Condition code
Neurological 303800 303800 0 0
Neurodegenerative diseases
Musculoskeletal 303815 303815 0 0
Other muscular and skeletal disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants in the study will be randomised in 2 groups: the training group (TRAIN) and the control group (CTRL).

TRAINING GROUP - TRAIN
Patients in TRAIN will visit the Victoria University Clinical Exercise Rehabilitation Clinic, Footscray Park Campus, Footscray (VIC), 3 times a week for 12 weeks. The training will be supervised by medical doctors specialized in Sports Medicine and Neurology, Exercise Physiologists and Students in the Master of Clinical Exercise and Rehabilitation at Victoria University. The training will be fully supervised with a patient/therapist ratio of 1:1. Each session, of 1 h duration, will be characterised by:
- 15 min of cycling at moderate intensity, e.g. at 50% of maximal aerobic capacity (VO2peak);
- 25 min of strength exercises at 60% of 1 repetition maximum (extrapolated from the 10RM test). One set of 10 repetitions of upper and lower body exercises on isotonic machines will be realised;
- 10 min of balance exercises;
- 10 min of stretching exercises.

Following the ability of each patient, the training will be adapted in the best way to him. The exercise physiologists will be able to adapt the exercises following the ability of the patients, but maintaining the scope (i.e. ameliorate the strength of a specific muscle group) and the quantity and intensity of the specific exercise. In fact, because the intensity of the training is relative, all patients will realise the same percentage of their maximal strength or aerobic capacity.

The adherence to the training program will be assessed by the investigators at the end of the 12 weeks of training. It will be explained to the patients before their consent, the importance of their participation to the training session for the outcomes of this study. The day and time of the training session will be decided together with the patient and it will be given to the patients the maximal possible freedom in the choice of the time of the day/day of the week for training. It will be asked to the patients to communicate to the exercise physiologist if they cannot participate to the training session and if they wish to communicate also the reason of their absence.

Each participant will perform 6 test sessions (test 1, test 2 and test 3): 3 before and 3 after 12 weeks of training. Test 1 will be performed at Sunshine Hospital, St Albans (VIC), and Test 2 and 3 at Victoria University, Footscray Park, Footscray (VIC). All testing sessions will be supervised at least by a medical doctor and an exercise physiologist.
Test 1. A medical doctor will administrate to the participants the ALSFRS-R scale and McGill Quality of Life and Brief Pain Inventory questionnaires. Successively, the patients will perform a cardiopulmonary exercise testing on a cycle ergometer, under medical supervision and with 12-lead electrocardiography monitoring. A small probe will be positioned on the belly of the vastus lateralis muscle to evaluate the maximal capacity of the muscle to extract O2 by Near-Infrared Spectroscopy (NIRS). Blood lactate will be determined on capillary blood samples obtained from an ear lobe, at rest and at 1, 3, 5 and 7 min after the termination of the maximal exercise. At the end of the exercise, a transient leg ischemia will be also performed by pressure cuff inflation (at about 300 mmHg) at the base of the thigh, for a few minutes (3-5 min).
Test 2: Patients will return to the laboratory to perform the "Timed Up and Go" test, a measure of functional capacity that incorporates balance, strength and mobility. Successively, the patients will perform the 10 repetitions maximum (10RM) test, to assess the strength of some lower and upper body muscle groups. 10RM is defined as the load that the subject is able to lift no more than 10 times.
Test 3. Patients will perform the "6 minutes walking test". Successively, the patients will perform the 10 repetitions maximum (10RM) test, to assess the strength of the remaining lower and upper body muscle groups. The electromyographyc activity of the abductor pollicis will be also evaluated.
The 10RM will be also evaluated after 6 weeks of training, and the weight lifted by patients during training will be recalculated.
Intervention code [1] 298945 0
Treatment: Other
Intervention code [2] 298958 0
Lifestyle
Comparator / control treatment
Control group – CTRL
Patients in CTRL will continue their standard of care during all the duration of the study. In example, patients will continue their physiotherapy (such as passive stretching exercises, etc), if it was recommended by their physiotherapist, or if not, they will continue their usual everyday activities.
Each participant will perform 6 test sessions (test 1, test 2 and test 3): 3 before and 3 after 12 weeks of standard of care. Test 1 will be performed at Sunshine Hospital, St Albans (VIC), and Test 2 and 3 at Victoria University, Footscray Park, Footscray (VIC). All testing sessions will be supervised at least by a medical doctor and an exercise physiologist.
Test 1. A medical doctor will administrate to the participants the ALSFRS-R scale and McGill Quality of Life and Brief Pain Inventory questionnaires. Successively, the participants will perform a cardiopulmonary exercise testing on a cycle-ergometer, under medical supervision and with 12-lead electrocardiography monitoring. A small probe will be positioned on the belly of the vastus lateralis muscle to evaluate the maximal capacity of the muscle to extract O2 by Near-Infrared Spectroscopy (NIRS). Blood lactate will be determined on capillary blood samples obtained from an ear lobe, at rest and at 1, 3, 5 and 7 min after the termination of the maximal exercise. At the end of the exercise, a transient leg ischemia will be also performed by pressure cuff inflation (at about 300 mmHg) at the base of the thigh, for a few minutes (3-5 min).
Test 2: Patients will return to the laboratory to perform the "Timed Up and Go" test, a measure of functional capacity that incorporates balance, strength and mobility. Successively, the patients will perform the 10 repetitions maximum (10RM) test, to assess the strength of some lower and upper body muscle groups. 10RM is defined as the load that the subject is able to lift no more than 10 times.
Test 3. Patients will perform the "6 minutes walking test". Successively, the patients will perform the 10 repetitions maximum (10RM) test, to assess the strength of the remaining lower and upper body muscle groups. The electromyographyc activity of the abductor pollicis will be also evaluated.
The 10RM will be also evaluated after 6 weeks of standard of care.
Control group
Active

Outcomes
Primary outcome [1] 303160 0
Mean change in maximal aerobic capacity (VO2peak) evaluated via a metabolic cart during a graded cardiopulmonary exercise testing to exhaustion on a cycle ergometer
Timepoint [1] 303160 0
Baseline and 12 weeks after the commencement of exercise training
Primary outcome [2] 303161 0
Mean change in maximal strength of the leg extensors (particularly the quadriceps muscle) evaluated on a leg extension machine. The patients is sitting on a chair and extend (from a bending position) both legs at the same time, and then lower them back to the starting position. The strength will be evaluated as the maximal weight lifted by the patient no more than 10 times (10RM) .
Timepoint [2] 303161 0
Baseline, 6 weeks and 12 weeks after the commencement of exercise training
Primary outcome [3] 303162 0
Mean change in maximal capacity of muscle oxygen extraction, as evaluated during a graded cardiopulmonary exercise test on a cycle ergometer, by Near Infrared Spectroscopy with a small probe positioned on the belly of the vastus lateralis muscle.
Timepoint [3] 303162 0
Baseline and 12 weeks after the commencement of exercise training
Secondary outcome [1] 338073 0
Mean change in physical function, evaluated by the "6 minutes walking test". The patient will walk at his own speed for 6min on a flat, hard surface. The distance that the patient can cover in this time will be recorded.
Timepoint [1] 338073 0
Baseline and 12 weeks after the commencement of exercise training
Secondary outcome [2] 338079 0
Mean change in physical function, as evaluated by "Timed Up and Go" test. The patients will rise from a chair, walk 3 meters, turn around, walk back to the chair and sit down. The time spent for this activity will be recorded.
Timepoint [2] 338079 0
Baseline and 12 weeks after the commencement of exercise training
Secondary outcome [3] 338080 0
Mean change in the ALS functional rating scale revisited (ALSFRS-R)
Timepoint [3] 338080 0
Baseline and 12 weeks after the commencement of exercise training
Secondary outcome [4] 338087 0
Assessment of quality of life using McGill Quality of Life questionnaire
Timepoint [4] 338087 0
Baseline and 12 weeks after the commencement of exercise training

Eligibility
Key inclusion criteria
- Patients with definite, probable or possible amyotrophic lateral sclerosis (based on El Escorial Criteria)
- Age: >18 years old
- Patients able to understand and comply with the requirements of the entire study (i.e. cycle on a bicycle), and to give an informed consent
Minimum age
18 Years
Maximum age
No limit
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, severe heart, lung, renal and liver failure
- Women who are pregnant or breastfeeding
- Participation in pharmacological studies within the last 30 days before 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)
Allocation will be done by central .randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomised table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Calculation of sample size is based on the assessment of a main effect for group differences in maximal O2 uptake (VO2peak). An effect size (Cohen’s d) was calculated from the changes in our pilot data measures, assuming that the control group score changes will be equal to zero. This is conservative as we expect them to decline over time. It was assumed that all tests will be performed at an alpha of 0.05 and that the desired power is at least 0.80. With these assumptions, the total effective sample size necessary to achieve statistical significance for the VO2peak is 10 patients per group. With a dropout rate of ~30%, we will consider 13 participants in each group.

Differences in mean values in the same group (before and after training) will be evaluated with a paired two-tailed Student t-test (if the data are normally distributed).
Differences in mean values between groups (TRAIN vs. CTRL) will be evaluated with an unpaired two-tailed Student t-test (if the data are normally distributed).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
1/11/2017
Actual
21/05/2018
Date of last participant enrolment
Anticipated
23/12/2025
Actual
Date of last data collection
Anticipated
23/12/2025
Actual
Sample size
Target
26
Accrual to date
13
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8848 0
Sunshine Hospital - St Albans
Recruitment postcode(s) [1] 16983 0
3021 - St Albans

Funding & Sponsors
Funding source category [1] 297343 0
Charities/Societies/Foundations
Name [1] 297343 0
Perpetual IMPACT Philantrophy Grant
Country [1] 297343 0
Australia
Primary sponsor type
Individual
Name
Alessandra Ferri
Address
Victoria University
Footscray Park
Ballarat Road
Footscray 3011
VIC
Country
Australia
Secondary sponsor category [1] 296320 0
University
Name [1] 296320 0
Victoria University
Address [1] 296320 0
Footscray Park
Ballarat Road
Footscray 3011
VIC
Country [1] 296320 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298443 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 298443 0
Ethics committee country [1] 298443 0
Australia
Date submitted for ethics approval [1] 298443 0
30/08/2017
Approval date [1] 298443 0
05/10/2017
Ethics approval number [1] 298443 0
HREC/17/MH/285
Ethics committee name [2] 298447 0
Victoria University Human Research Ethics Committee
Ethics committee address [2] 298447 0
Ethics committee country [2] 298447 0
Australia
Date submitted for ethics approval [2] 298447 0
27/09/2017
Approval date [2] 298447 0
22/03/2018
Ethics approval number [2] 298447 0

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

Contacts
Principal investigator
Name 77110 0
Dr Alessandra Ferri
Address 77110 0
Victoria University
Footscray Park
Ballarat Road
Footscray
VIC 3011
Country 77110 0
Australia
Phone 77110 0
+61 3 9919 4756
Fax 77110 0
+61 3 9919 9480
Email 77110 0
[email protected]
Contact person for public queries
Name 77111 0
Alessandra Ferri
Address 77111 0
Victoria University
Footscray Park
Ballarat Road
Footscray
VIC 3011
Country 77111 0
Australia
Phone 77111 0
+61 3 9919 4756
Fax 77111 0
+61 3 9919 9480
Email 77111 0
[email protected]
Contact person for scientific queries
Name 77112 0
Alessandra Ferri
Address 77112 0
Victoria University
Footscray Park
Ballarat Road
Footscray
VIC 3011
Country 77112 0
Australia
Phone 77112 0
+61 3 9919 4756
Fax 77112 0
+61 3 9919 9480
Email 77112 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?
Individual non sensitive de-identified participant data underlying published results only will be available
When will data be available (start and end dates)?
Immediately following publication, no end date
Available to whom?
Case-by-case basis at the discretion of Principal Investigator
Available for what types of analyses?
For all purposes aiming to advance the research field
How or where can data be obtained?
Access subject to approval by Principal Investigator by emailing [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
19068Study protocol  [email protected]
19069Informed consent form  [email protected]
19070Ethical approval  [email protected]



Results publications and other study-related documents

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Documents added automatically
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