None listed
Conditions
Brief summary
Every day, two new Australians are diagnosed with motor neuron disease (MND) - a fatal neurodegenerative disease characterised by the progressive degeneration and death of motor neurons that leads to muscle weakness, physical disability, and ultimately death. The aim of this project is to understand if exercise can slow the neurodegeneration in MND, by investigating the neuroprotective potential of 16 weeks of carefully prescribed exercise on the brain, spinal cord, and muscle of patients with MND. Participants enrolled in the study will be randomly allocated to a training (TRAIN) or control (CTRL) group. Participants in the TRAIN group will perform 16 weeks of exercise training, 3 times per week, at the Victoria University Clinical Exercise and Rehabilitation (VUCER) clinic in Footscray. Participants in the CTRL group will continue their standard of care. Before, at the end of the exercise training or standard of care period of 16 weeks, and at 24 weeks, which equates to 8 weeks following cessation of intervention, all participants will be evaluated with brain imaging (magnetic resonance imaging, MRI), neurophysiological (surface electromyography, EMG) and muscle strength measurements, aerobic fitness, respiratory and functional tests. Quality of life (QoL), fatigue and functional questionnaires will be also administered to all participants. In a subgroup of participants, resting needle biopsies will be obtained from the vastus lateralis muscle in the thigh, before and at the end of 16 weeks of intervention. We hypothesise that individuals who exercise will present a reduced motor neuron degeneration in the brain and spinal cord, and a preserved skeletal muscle mitochondrial function and content, with respect to individuals in the control treatment (standard of care). This will result in delaying the disease progression by maintaining strength, physical function and independence. This multimodal approach of investigating the neuroprotective effect of exercise in those with MND will provide a fundamentally new understanding that has the potential to alter the role of exercise in the treatment of MND, and could be used to identify new targets for neuroprotective therapeutics.
Interventions
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:
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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.
Sponsors
Victoria University
Study design
Allocation
Randomised controlled trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
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
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
Outcome results
None listed