Multiple Sclerosis
Conditions
Keywords
Exercise, Cognition, Neuroimaging, Rehabilitation, Connectivity
Brief summary
Cognitive dysfunction is frequent in patients with multiple sclerosis (MS) and to date, there are no available treatments to improve cognition in this patient population. Some evidence from animal studies and small clinical trials suggest that aerobic exercise might beneficially affect cognitive function in MS. The aim of this randomized-controlled trial is to explore if an aerobic exercise training program can enhance cognition in MS. In addition, we will employ neuroimaging markers to determine if exercise alters measures of brain structure and function. Patients will be randomly assigned to either a 3-months exercise program (bicycle ergometry, 2-3 session per week) or a waitlist control group. The primary endpoint of the study is a test of verbal learning and memory. Secondary endpoints include neuroimaging markers of functional and structural connectivity in the brain. We hypothesize that exercise will improve verbal learning and memory and beneficially affect measures of brain connectivity.
Detailed description
Background: Cognitive dysfunction is frequent in patients with multiple sclerosis (MS) and to date, there are no available treatments to improve cognition in this patient population. Some evidence from animal studies and small clinical trials suggest that aerobic exercise might beneficially affect cognitive function in MS. Aims: This study aims to explore the potential of an aerobic exercise program on brain structure and function in MS in a single-blind, randomized controlled phase IIa trial. We hypothesize that exercise will improve verbal learning and memory (primary endpoint) as well as induce changes in neuroimaging markers of structural and functional central nervous system (CNS) connectivity (secondary endpoints). Tertiary outcomes will include walking ability, motor function and coordination, as well as patient-based outcomes (depression, fatigue, and health-related quality of life). Design: This is a single-blind, randomized, controlled phase IIa trial with a parallel group design comparing 3 months of standardized aerobic exercise training (bicycle ergometry) to a waitlist control group (superiority framework). The allocation ratio of exercise to waitlist control is 1:1 with a sample size of n=60.
Interventions
BEHAVIORALAerobic Exercise
3-months exercise program tailored to the individual level of aerobic fitness. Patients will exercise on a bicycle ergometer (2-3 session per week) according to a predefined training plan with increasing duration and intensity
Sponsors
German Federal Ministry of Education and Research
Universitätsklinikum Hamburg-Eppendorf
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Relapsing-remitting multiple sclerosis according to McDonald criteria * Currently in remission * Disease duration \< 10 years * Low to moderate physical disability (EDSS 0-3.5) * On stable immunotherapy (\>3 months) or without any planned treatment for the next year
Exclusion criteria
* Patients who are not able to understand the study concept due to severe cognitive deficits or psychiatric comorbidity * Patients currently taking psychoactive drugs * Patients unable to undergo aerobic exercise training for medical reasons * Patients with active disease or uncertain stability under current immunomodulatory therapy (as judged by the treating neurologist) * Patients with implants or body modifications (e.g. dental implants, piercings, tattoos, pacemakers etc.) which might interfere with MEG and MRI assessments * Patients unable to travel to the study center 2-3 times a week for the duration of the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Verbal Learning and Memory | Baseline and at Month 3 (end of intervention) | Verbal Learning and Memory will be assessed with the Verbal Learning and Memory Test (VLMT) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Functional Connectivity | Baseline and at Month 3 (end of intervention) | Functional connectivity of CNS networks will be assessed by resting-state functional magnetic resonance imaging (rs fMRI) and resting-state magnetoencephalography (rs MEG) |
| Change in Structural Connectivity | Baseline and at Month 3 (end of intervention) | Structural connectivity and integrity of CNS networks will be assessed by diffusion tensor imaging (DTI) as well as measures of gray matter density using magnetic resonance imaging (MRI) |
| Change in Neuropsychological Function | Baseline and at Month 3 (end of intervention) | Neuropsychological function will be assessed using a standardized battery covering the following domains: visuospatial learning and memory, attention, processing speed, working memory, and social cognition |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Patient-Reported Outcomes | Baseline and at Month 3 (end of intervention) | Patient-reported outcomes will be assessed for depressive symptoms (IDS-30SR), fatigue (FSMC), quality of life (HAQUAMS), and walking (MSWS-12) |
| Change in Walking Ability | Baseline and at Month 3 (end of intervention) | Walking ability will be assessed using the six-minute-walk test (6MWT) as well as Actibelt accelerometry |
Countries
Germany
Outcome results
None listed