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

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.