Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial

Robert W Motl; Brian M Sandroff; Roberto S Hernandez; Maria Pia Amato; Giampaolo Brichetto; Jeremy Chataway; Nancy D Chiaravalloti; Gary Cutter; Ulrik Dalgas; John DeLuca; Rachel Farrell; Peter Feys; Massimo Filippi; Jennifer Freeman; Matilde Inglese; Cecilia Meza; Maria A Rocca; Amber Salter; Anthony Feinstein; CogEx Research Team

doi:10.1177/20552173241301030

Heterogeneity of aerobic fitness changes with exercise training in progressive multiple sclerosis: Secondary, exploratory analysis of data from the CogEx trial

Mult Scler J Exp Transl Clin. 2024 Dec 5;10(4):20552173241301030. doi: 10.1177/20552173241301030. eCollection 2024 Oct-Dec.

Authors

Robert W Motl¹, Brian M Sandroff², Roberto S Hernandez³, Maria Pia Amato⁴, Giampaolo Brichetto⁵, Jeremy Chataway⁶, Nancy D Chiaravalloti², Gary Cutter⁷, Ulrik Dalgas⁸, John DeLuca², Rachel Farrell⁶, Peter Feys⁹, Massimo Filippi¹⁰, Jennifer Freeman¹¹, Matilde Inglese¹², Cecilia Meza¹³, Maria A Rocca¹⁰, Amber Salter³, Anthony Feinstein¹³; CogEx Research Team

Affiliations

¹ Department of Kinesiology and Nutrition, University of Illinois Chicago, Chicago, IL, USA.
² Kessler Foundation, West Orange, NJ, USA.
³ Department of Neurology, Section on Statistical Planning and Analysis, UT Southwestern Medical Center, Dallas, TX, USA.
⁴ Department NEUROFARBA, Section Neurosciences, University of Florence, Florence, Italy.
⁵ Scientific Research Area, Italian Multiple Sclerosis Foundation (FISM), Genoa, Italy.
⁶ Queen Square Multiple Sclerosis Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, Faculty of Brain Sciences, University College London, London, UK.
⁷ Department of Biostatistics, University of Alabama, Birmingham, AL, USA.
⁸ Exercise Biology, Department of Public Health, Aarhus University, Aarhus, Denmark.
⁹ REVAL, Faculty of Rehabilitation Sciences, Hasselt University, Diepenbeek, Belgium.
¹⁰ Neuroimaging Research Unit, Division of Neuroscience, IRCCS San Raffaele Scientific Institute, Milan, Italy.
¹¹ Faculty of Health, School of Health Professions, University of Plymouth, Devon, UK.
¹² Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
¹³ Department of Psychiatry, University of Toronto and Sunnybrook Health Sciences Centre, Toronto, ON, Canada.

Abstract

Background: There is heterogeneity of aerobic fitness (VO_2peak) changes with a standardized exercise training stimulus in the general population (i.e. some participants demonstrate improvements, others no change, and some a reduction in VO_2peak).

Objectives: This secondary, exploratory analysis of data examined the heterogeneity of VO_2peak responses and possible correlates among persons with progressive multiple sclerosis (PMS) from the CogEx trial.

Methods: CogEx was a multi-site, multi-arm, randomized, double-blinded, and sham-controlled trial undertaken by 11 sites in six different countries. Participants were randomized into one of four conditions with different combinations of exercise training and cognitive rehabilitation including respective sham conditions. The analysis focuses primarily on VO_2peak change for the pooled exercise training intervention conditions compared with the pooled sham exercise control conditions.

Results: Waterfall plots for change in VO_2peak suggested greater heterogeneity with exercise training than sham, and the proportions of difference in VO_2peak change (i.e. improvement/worsening) were significantly different between exercise training and sham conditions(p < 0.05). The multivariable analysis indicated that lower baseline VO_2peak (p < 0.001) was the only statistically significant correlate of increases in VO_2peak with exercise training.

Conclusion: Our results highlight the heterogeneity of change in VO_2peak with exercise training that is correlated with initial aerobic capacity in PMS, and such results may inform hypothesis testing in future clinical trials of exercise training.

Keywords: Exercise; heterogeneity; progressive MS.