A randomized controlled trial of resistance and endurance exercise in amyotrophic lateral sclerosis

Abstract

Objective: Evaluate the safety and tolerability of resistance and endurance exercise in ALS participants as measured by their ability to complete this six-month study. Methods: Participants were randomized to Resistance, Endurance, or Stretching/Range of Motion (SROM the exercise regimen prescribed for most ALS patients) exercises. All exercises were performed at home with an individualized regimen designed by a physical therapist trained in ALS management. Primary outcome measures were tolerability of the exercises at 24 weeks defined by 50% of participants completing at least 50% of the prescribed exercise regimen. Secondary outcome measures included the ALSFRS-R, pulmonary FVC, and other measures of ALS function. Results: At 12 and 24 weeks, all three exercise regimens were tolerated according to our pre-specified criteria. Compliance to the prescribed exercise regimen was the highest in the resistance and SROM arms of the study. All three forms of exercise were considered safe as there were no differences in the rates of disease progression among groups. There were no differences in the secondary outcome measures and feasibility for evaluating these measures was successful. In a post-hoc analysis, there was a trend towards fewer falls in the Resistance and Endurance groups. Conclusions: This study demonstrates that SROM, resistance, and endurance exercise are all safe to be performed with the specified regimen without any worsening of outcomes as related to ALS function. All three forms of exercise were tolerated with resistance and SROM exercises showing the highest compliance over the 24 week-period.

Keywords:

• ALS
• tolerability
• benefit
• motor neuron disease
• clinical trial

Acknowledgements

Co-investigators and Northeast ALS Consortium: Vanina Dal Bello Haas (McMaster University, Advisor), Julaine Florence (Washington University, Advisor), and Mark Tarnopolsky (McMaster University, Advisor). The Northeast ALS Consortium: Robert Baloh (Cedars Sinai, Site Investigator), James Berry (Massachusetts General Hospital, Site Investigator), Richard Lewis (Cedars Sinai Medical Center, Site Investigator), Elizabeth Mosmiller (Johns Hopkins University, Clinical Evaluator), Kelly Casey (Johns Hopkins University, Occupational Therapist), Amy Swartz Ellrodt (Massachusetts General Hospital, Study Coordinator & Physical Therapist), Owen O’Connor (Massachusetts General Hospital, Study Coordinator) Kellen Haley (Massachusetts General Hospital, Study Coordinator), Pat Andres (Massachusetts General Hospital, Physical Therapist), Cynthia Lary (Carolinas Medical Center, Study Coordinator), Scott Holsten (Carolinas Medical Center, Clinical Evaluator), K. Ashley Fetterman (Cedars-Sinai Medical Center, Study Coordinator). Erik Pioro (Cleveland Clinic, Data and Safety Monitor), Haining Li (Massachusetts General Hospital, Data Management), K. Jane Barkan (Barrows Neurological Institute, Site Monitor), Jeremy Shefner (Barrows Neurological Institute, Director of Site Monitoring).

Declaration of interest

Lora Clawson: Nothing to disclose.

Merit Cudkowicz: Consultant for Mitsubishi Tanabe, Cytokinetics, Biohaven, Voyager, and DSMB Chair Lilly.

Lisa Krivickas: Nothing to disclose.

David Schoenfeld: Consultant to: Brainstorm, Mistubishi Pharma, Pfizer, Orthozyme.

Benjamin Rix Brooks: Consultant for Mitsubishi Tanabe, Cytokinetics, Santhera, Biogen, Avanir.

Mohammed Sanjak: Nothing to disclose.

Nazem Atassi: Consultant for Biogen and MT Pharma.

Hong Yu: Nothing to disclose.

Amy Swartz: Nothing to disclose.

Gabrielle Steinhorn: Nothing to disclose.

Alpa Uchil: Nothing to disclose.

Kristen Riley: Nothing to disclose.

Nicholas J. Maragakis– Scientific Advisory Board, Above and Beyond, LLC, Consultant to Biogen/Idec, Biohaven Pharmaceuticals, Cytokinetics, Q Therapeutics, Inc., Navigant, Izumi.

Supplementary material available online

Additional information

Funding

This study was funded by the ALS Association Grant #1489 as well as the William Gray Smith Fund at Johns Hopkins.