Aerobic Exercise Training in Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to compare the safety and the effects of moderate-intensity aerobic endurance training to those of an usual physical therapy intervention on exercise capacity and quality of life in patients with amyotrophic lateral sclerosis (ALS).

Detailed Description
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Scarce evidence is available regarding aerobic exercise training of patients with ALS. Some studies using transgenic mouse models of familial ALS have shown markedly slowed disease progression, improved functional capacity, and extension of survival in animals undergoing aerobic exercise training. In humans, only one non-randomized study has shown that moderate-intensity aerobic exercise training was of little beneficial effect in a small group of patients with Kennedy disease, a rare X-linked progressive neuromuscular disease involving lower motorneurons, presenting a pathophysiological picture quite different from that of ALS. To the best of our knowledge, the safety and the effects of aerobic exercise training on functional capacity and quality of life of patients with ALS have not been systematically evaluated as yet in a randomized, controlled trial with an adequate sample size.

Official Title
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Exercise traiNing in Amyotrophic Lateral Sclerosis: a ranDomized Trial Comparing Home-based Aerobic endUrance tRAiNing vs. Usual physiCal Therapy intErvention

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Other: Aerobic exercise training
* Other: Standard physical therapy (Stretching/Range-of-motion)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of definite ALS, probable ALS, or probable-laboratory supported ALS according to the El Escorial criteria or diagnosis of progressive muscular atrophy. Ability to perform a baseline symptom-limited cardiopulmonary exercise test with attainment of peak power and respiratory exchange ratio of >= 50 W and >= 1.00, respectively. Time since symptoms onset <= 18 months. Forced vital capacity >= 70% of predicted. Informed written consent. Exclusion Criteria: Coexisting neurological disease. Coexisting extra-neurological disease significantly affecting exercise capacity. Coexisting malignancy. Ongoing/planned pregnancy. Involvement in formal endurance and/or strength training program. Enrolment in any other clinical trial. Cognitive impairment.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aerobic exercise training<br> | Other: Aerobic exercise training<br>* Intensity: heart rate corresponding to 40% peak VO2. Frequency: 5 sessions/week. Duration: 5 min warm-up + 20 min training + 5 min cool-down during the 1st month; 5 min warm-up + 30 min training + 5 min cool-down during the 2nd and 3rd month<br>|
| Active Comparator: Standard physical therapy<br> | Other: Standard physical therapy (Stretching/Range-of-motion)<br>* Intensity: N/A. Frequency: 5 sessions/week. Duration: 5 min warm-up + 20 min training + 5 min cool-down during the 1st month; 5 min warm-up + 30 min training + 5 min cool-down during the 2nd and 3rd month<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in peak oxygen consumption (peak VO2) | Evaluate the effects of aerobic training on peak VO2, as assessed by cardiopulmonary exercise testing | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aerobic training safety and tolerability | Evaluate aerobic training safety and tolerability in terms of adverse events incidence and adherence to training program | 3 months | 
| Change from baseline in quality of life | Evaluate the effects of aerobic training on quality of life, as assessed by McGill questionary | 3 months | 
| Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score | Evaluate the effects of aerobic training on the ALSFRS-R score | 3 months | 
| Change from baseline in lower limbs muscle strength | Evaluate the effects of aerobic training on isometric muscle strength of lower limbs, as assessed by isometric dynamometry | 3 months | 
| Change from baseline in upper and lower motor neurons function at the upper and lower limbs level | Evaluate the effects of aerobic training on upper and lower motor neurons function at the upper and lower limbs level, as determined by compound muscle action potential and neurophysiological index and motor evoked potentials | 3 months | 
| Change from baseline in ventilatory function | Evaluate the effects of aerobic training on ventilatory function, as assessed by spirometry and measurement of maximal inspiratory and expiratory pressures | 3 months | 
| Change from baseline in circulating inflammatory markers, growth factors and descriptors of skeletal muscle damage | Evaluate the effects of aerobic training on circulating inflammatory markers and growth factors (CRP, TNF-alfa, IL-6, Angiogenin, Angiopoietin 1 and 2, Thrombospondin, VEGF, BDNF, IGF-1) and markers of skeletal muscle damage (CPK) | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Amyotrophic lateral sclerosis, Aerobic training, Peak oxygen consumption, Quality of life