Aerobic Exercise Training in Amyotrophic Lateral Sclerosis (ENDURANCE)

• ClinicalTrials.gov Identifier: NCT01650818
• Recruitment Status: Unknown
• First Posted: July 26, 2012
• Last Update Posted: September 10, 2013
• Sponsor: Fondazione Salvatore Maugeri
• Information provided by (Responsible Party): Alessandro Mezzani, Fondazione Salvatore Maugeri

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Amyotrophic Lateral Sclerosis	Other: Aerobic exercise training; Other: Standard physical therapy (Stretching/Range-of-motion)	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Exercise traiNing in Amyotrophic Lateral Sclerosis: a ranDomized Trial Comparing Home-based Aerobic endUrance tRAiNing vs. Usual physiCal Therapy intErvention
• Study Start Date: January 2012
• Estimated Primary Completion Date: June 2014
• Estimated Study Completion Date: June 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Change from baseline in peak oxygen consumption (peak VO2) [ Time Frame: 3 months ]
   Evaluate the effects of aerobic training on peak VO2, as assessed by cardiopulmonary exercise testing

Secondary Outcome Measures :

1. Aerobic training safety and tolerability [ Time Frame: 3 months ]
   Evaluate aerobic training safety and tolerability in terms of adverse events incidence and adherence to training program
2. Change from baseline in quality of life [ Time Frame: 3 months ]
   Evaluate the effects of aerobic training on quality of life, as assessed by McGill questionary
3. Change from baseline in Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R) score [ Time Frame: 3 months ]
   Evaluate the effects of aerobic training on the ALSFRS-R score
4. Change from baseline in lower limbs muscle strength [ Time Frame: 3 months ]
   Evaluate the effects of aerobic training on isometric muscle strength of lower limbs, as assessed by isometric dynamometry
5. Change from baseline in upper and lower motor neurons function at the upper and lower limbs level [ Time Frame: 3 months ]
   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
6. Change from baseline in ventilatory function [ Time Frame: 3 months ]
   Evaluate the effects of aerobic training on ventilatory function, as assessed by spirometry and measurement of maximal inspiratory and expiratory pressures
7. Change from baseline in circulating inflammatory markers, growth factors and descriptors of skeletal muscle damage [ Time Frame: 3 months ]
   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)

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Contacts

Contact: Fabrizio Pisano, MD; +39-0322-884723; fabrizio.pisano@fsm.it

Locations

Italy

Fondazione Salvatore Maugeri, IRCCS - Scientific Institute of Veruno; Recruiting

Veruno, Italy, 28010

Contact: Alessandro Mezzani, MD, FESC 3403119299 alessandro.mezzani@fsm.it

Principal Investigator: Alessandro Mezzani, MD, FESC

Sponsors and Collaborators

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

More Information

Publications:

Mezzani A, Pisano F, Cavalli A, Tommasi MA, Corrà 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.

• Responsible Party: Alessandro Mezzani, MD, FESC, Fondazione Salvatore Maugeri
• ClinicalTrials.gov Identifier: NCT01650818
• Other Study ID Numbers: CEC641
• First Posted: July 26, 2012
• Last Update Posted: September 10, 2013
• Last Verified: September 2013

Keywords provided by Alessandro Mezzani, Fondazione Salvatore Maugeri:

Amyotrophic lateral sclerosis; Aerobic training; Peak oxygen consumption; Quality of life

Additional relevant MeSH terms:

Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis; Pathologic Processes; Neurodegenerative Diseases; Nervous System Diseases; Neuromuscular Diseases; Spinal Cord Diseases; Central Nervous System Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Metabolic Diseases