Aerobic Exercise Training in Amyotrophic Lateral Sclerosis (ENDURANCE)

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

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).

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Aerobic exercise training; Other: Standard physical therapy (Stretching/Range-of-motion)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fabrizio Pisano, MD; Phone Number: +39-0322-884723; Email: fabrizio.pisano@fsm.it

Study Locations

• Italy
  • Veruno, Italy, 28010
    • Recruiting
    • Fondazione Salvatore Maugeri, IRCCS - Scientific Institute of Veruno
    • Contact: Alessandro Mezzani, MD, FESC; Phone Number: 3403119299; Email: alessandro.mezzani@fsm.it
    • Principal Investigator: Alessandro Mezzani, MD, FESC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Aerobic exercise training	Other: Aerobic exercise training; 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
ACTIVE_COMPARATOR: Standard physical therapy	Other: Standard physical therapy (Stretching/Range-of-motion); 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fondazione Salvatore Maugeri
• Investigators: Principal Investigator: Alessandro Mezzani, MD, Fondazione Salvatore Maugeri, IRCCS - Scientific Institute of Veruno; Study Director: Fabrizio Pisano, MD, Fondazione Salvatore Maugeri, IRCCS - Scientific Institute of Veruno

Publications and helpful links

General Publications

• Mezzani A, Pisano F, Cavalli A, Tommasi MA, Corra U, Colombo S, Grassi B, Marzorati M, Porcelli S, Morandi L, Giannuzzi P. Reduced exercise capacity in early-stage amyotrophic lateral sclerosis: Role of skeletal muscle. Amyotroph Lateral Scler. 2012 Jan;13(1):87-94. doi: 10.3109/17482968.2011.601463. Epub 2011 Aug 11.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (ANTICIPATED): June 1, 2014
• Study Completion (ANTICIPATED): June 1, 2014

Study Registration Dates

• First Submitted: July 24, 2012
• First Submitted That Met QC Criteria: July 25, 2012
• First Posted (ESTIMATE): July 26, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): September 10, 2013
• Last Update Submitted That Met QC Criteria: September 8, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Quality of life; Aerobic training; Amyotrophic lateral sclerosis; Peak oxygen consumption
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CEC641