TY - JOUR
T1 - Protocol for an exploratory, randomised, single-blind clinical trial of aerobic exercise to promote remyelination in multiple sclerosis
AU - Wooliscroft, Lindsey
AU - McCoy, Sharon
AU - Hildebrand, Andrea
AU - Rooney, William
AU - Oken, Barry S.
AU - Spain, Rebecca Irene
AU - Kuehl, Kerry S.
AU - Bourdette, Dennis
AU - Cameron, Michelle
N1 - Publisher Copyright:
© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.
PY - 2023/1/3
Y1 - 2023/1/3
N2 - Introduction There is an urgent need for remyelinating therapies that restore function in people with multiple sclerosis (pwMS). Aerobic exercise is a promising remyelinating strategy because it promotes remyelination in animal models both independently and synergistically with medications. Here, in this study, we present an innovative, randomised, single-blind, clinical trial designed to explore: the relationship between demyelination and mobility (part 1), and if 24 weeks of aerobic exercise promotes remyelination in pwMS (part 2). Methods and analysis Sedentary participants (n=60; aged 18-64 years) with stable MS will undergo a baseline visit with the following outcomes to assess associations between demyelination and mobility (part 1): spinal cord demyelination (somatosensory-evoked potentials, SSEPs), mobility (6-Minute Timed Walk, Timed 25-Foot Walk, Timed Up and Go, 9-Hole Peg Test) and patient-reported outcomes (PROs). After baseline testing, participants with significantly prolonged SSEP latency will advance to the clinical exercise trial (part 2) and will be randomised 1:1 to active or control conditions for 24 weeks. The active condition will be aerobic stationary cycling three times per week with graded virtual supervision. The control condition will be monthly virtual MS symptom education groups (six sessions). SSEP latency (remyelination endpoint), mobility outcomes and PROs will be measured at 12 and 24 weeks in all clinical trial participants. A subset of 11 active and 11 control participants will undergo a brain MRI with quantitative T 1 myelin water fraction at baseline and 24 weeks (exploratory remyelination endpoint). Ethics and dissemination Ethical approval was obtained from the Oregon Health & Science University Institutional Review Board (#21045). Dissemination of findings will include peer-reviewed publications, conference presentations and media releases. The proposed study will inform the feasibility, study design and sample size for a fully powered clinical trial of aerobic exercise to promote remyelination in pwMS. Trial registration number NCT04539002.
AB - Introduction There is an urgent need for remyelinating therapies that restore function in people with multiple sclerosis (pwMS). Aerobic exercise is a promising remyelinating strategy because it promotes remyelination in animal models both independently and synergistically with medications. Here, in this study, we present an innovative, randomised, single-blind, clinical trial designed to explore: the relationship between demyelination and mobility (part 1), and if 24 weeks of aerobic exercise promotes remyelination in pwMS (part 2). Methods and analysis Sedentary participants (n=60; aged 18-64 years) with stable MS will undergo a baseline visit with the following outcomes to assess associations between demyelination and mobility (part 1): spinal cord demyelination (somatosensory-evoked potentials, SSEPs), mobility (6-Minute Timed Walk, Timed 25-Foot Walk, Timed Up and Go, 9-Hole Peg Test) and patient-reported outcomes (PROs). After baseline testing, participants with significantly prolonged SSEP latency will advance to the clinical exercise trial (part 2) and will be randomised 1:1 to active or control conditions for 24 weeks. The active condition will be aerobic stationary cycling three times per week with graded virtual supervision. The control condition will be monthly virtual MS symptom education groups (six sessions). SSEP latency (remyelination endpoint), mobility outcomes and PROs will be measured at 12 and 24 weeks in all clinical trial participants. A subset of 11 active and 11 control participants will undergo a brain MRI with quantitative T 1 myelin water fraction at baseline and 24 weeks (exploratory remyelination endpoint). Ethics and dissemination Ethical approval was obtained from the Oregon Health & Science University Institutional Review Board (#21045). Dissemination of findings will include peer-reviewed publications, conference presentations and media releases. The proposed study will inform the feasibility, study design and sample size for a fully powered clinical trial of aerobic exercise to promote remyelination in pwMS. Trial registration number NCT04539002.
KW - Multiple sclerosis
KW - REHABILITATION MEDICINE
KW - SPORTS MEDICINE
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U2 - 10.1136/bmjopen-2022-061539
DO - 10.1136/bmjopen-2022-061539
M3 - Article
C2 - 36596632
AN - SCOPUS:85145430716
SN - 2044-6055
VL - 13
JO - BMJ open
JF - BMJ open
IS - 1
M1 - e061539
ER -