Martin Langeskov-Christensen1,2,3,4,5,6,7,8,9,10, Lars Grøndahl Hvid11,12,13,14,15,16,17,18,19,20, Mikkel Karl Emil Nygaard11,12,13,14,15,16,17,18,19,20, Steffen Ringgaard11,12,13,14,15,16,17,18,19,20, Henrik Boye Jensen11,12,13,14,15,16,17,18,19,20, Helle Hvilsted Nielsen11,12,13,14,15,16,17,18,19,20, Thor Petersen11,12,13,14,15,16,17,18,19,20, Egon Stenager11,12,13,14,15,16,17,18,19,20, Simon Fristed Eskildsen11,12,13,14,15,16,17,18,19,20, Ulrik Dalgas11,12,13,14,15,16,17,18,19,20. 1. M Langeskov-Christensen, LG Hvid, U Dalgas, Section for Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark; mach@ph.au.dk. 2. MKE Nygaard, SF Eskildsen, Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; mach@ph.au.dk. 3. S Ringgaard, MR Research Centre, Aarhus University Hospital, Aarhus, Denmark;HB Jensen, Brain and Nerve Diseases, Department of Neurology, Lillebaelt Hospital, Kolding, Denmark; mach@ph.au.dk. 4. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; mach@ph.au.dk. 5. HH Nielsen Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; mach@ph.au.dk. 6. Department of Neurology, Odense University Hospital, Odense, Denmark; mach@ph.au.dk. 7. BRIDGE-Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, Denmark; mach@ph.au.dk. 8. T Petersen, The Multiple Sclerosis Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; mach@ph.au.dk. 9. E Stenager, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark; mach@ph.au.dk. 10. E Stenager, MS-Clinic of Southern Jutland (Sønderborg, Kolding, Esbjerg), Department of Neurology, Hospital of Southern Denmark, Sønderborg, Denmark mach@ph.au.dk. 11. M Langeskov-Christensen, LG Hvid, U Dalgas, Section for Sport Science, Department of Public Health, Aarhus University, Aarhus, Denmark. 12. MKE Nygaard, SF Eskildsen, Center of Functionally Integrative Neuroscience, Department of Clinical Medicine, Aarhus University, Aarhus, Denmark. 13. S Ringgaard, MR Research Centre, Aarhus University Hospital, Aarhus, Denmark;HB Jensen, Brain and Nerve Diseases, Department of Neurology, Lillebaelt Hospital, Kolding, Denmark. 14. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. 15. HH Nielsen Department of Neurobiology Research, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark. 16. Department of Neurology, Odense University Hospital, Odense, Denmark. 17. BRIDGE-Brain Research-Inter-Disciplinary Guided Excellence, Department of Clinical Research, University of Southern Denmark, Odense, Denmark. 18. T Petersen, The Multiple Sclerosis Clinic, Department of Neurology, Aarhus University Hospital, Aarhus, Denmark. 19. E Stenager, Department of Regional Health Research, University of Southern Denmark, Odense, Denmark. 20. E Stenager, MS-Clinic of Southern Jutland (Sønderborg, Kolding, Esbjerg), Department of Neurology, Hospital of Southern Denmark, Sønderborg, Denmark.
Abstract
OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS). METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle. RESULTS:Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group. CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted. CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555. CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.
RCT Entities:
OBJECTIVE: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS). METHODS: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired MS patients aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle. RESULTS: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% CI -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O2/min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group. CONCLUSION: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted. CLINICALTRIALS REGISTRATION: ClinicalTrials.gov identifier NCT02661555. CLASSIFICATION OF EVIDENCE: This study provides level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate.
Authors: Morten Riemenschneider; Lars G Hvid; Steffen Ringgaard; Mikkel K E Nygaard; Simon F Eskildsen; Thor Petersen; Egon Stenager; Ulrik Dalgas Journal: BMJ Open Date: 2021-01-12 Impact factor: 2.692
Authors: Alan J Thompson; William Carroll; Olga Ciccarelli; Giancarlo Comi; Anne Cross; Alexis Donnelly; Anthony Feinstein; Robert J Fox; Anne Helme; Reinhard Hohlfeld; Robert Hyde; Pamela Kanellis; Douglas Landsman; Catherine Lubetzki; Ruth Ann Marrie; Julia Morahan; Xavier Montalban; Bruno Musch; Sarah Rawlings; Marco Salvetti; Finn Sellebjerg; Caroline Sincock; Kathryn E Smith; Jon Strum; Paola Zaratin; Timothy Coetzee Journal: Mult Scler Date: 2021-12-01 Impact factor: 6.312