Multiple Sclerosis, Neuroinflammatory Diseases
Conditions
Keywords
multiple sclerosis, physical activity, depression, exercise intervention, biomarkers, irisin, brain-derived neurotrophic factor BDNF, randomized controlled trial, feasibility study, home-based exercise, youth, children, pediatric, brain and mental health
Brief summary
This multi-center, randomized controlled feasibility trial will assess a 20-week home-based exercise intervention in youth with Multiple Sclerosis (MS). The goal is to determine the feasibility of conducting a larger, definitive trial on exercise training as a non-pharmacological approach to improve disease outcomes in this population. Participants will be randomized to either an Exercise Training group or a Mobility and Flexibility Training group. The investigators will evaluate differences between the two groups in physical activity levels, mediators of physical activity, and psychosocial outcomes. Assessments, including clinical exams, brain MRI, eye tracking, cognitive testing, blood draws, and questionnaires, will occur at baseline and after 20 weeks. Accelerometry will be done at baseline, 10 weeks, and 20 weeks to track physical activity. The primary objectives are to assess the feasibility of recruiting, retaining, and randomizing youth with MS and to evaluate adherence to the exercise intervention and coaching sessions. Exploratory objectives include examining changes in depressive symptoms, cognitive function, blood biomarkers (BDNF and irisin), brain volume, and fitness levels in response to the intervention. Approximately 40 participants will be enrolled from four sites in Canada and the United States. Primary outcomes include feasibility, acceptability, and fidelity measures. Exploratory outcomes include blood biomarkers, brain MRI, cognitive testing, and other neuropsychological measures.
Detailed description
Overview: This research study explores the potential of exercise as a non-pharmacological treatment for youth with Multiple Sclerosis (MS). The investigators are conducting a 20-week home-based exercise program to determine if it is feasible to implement this type of intervention in a larger trial in the future. Our ultimate goal is to understand how exercise might help improve both physical and mental health outcomes for youth with MS. Why This Study is Important: Multiple Sclerosis is a chronic disease that affects the brain and spinal cord, often leading to issues with movement, balance, vision, and other body functions. In young people, MS can have a significant impact on daily life, including mental health and cognitive abilities (such as memory and problem-solving). Medications can help manage symptoms, but there is growing interest in non-medication approaches, like exercise, to enhance the overall well-being of youth with MS. This study aims to investigate whether a structured exercise program can benefit physical fitness, mental health, and brain function in young people living with MS. Study Design: This feasibility trial will enroll approximately 40 participants from four different locations in Canada and the United States. These participants will be youth diagnosed with MS. Participants will be randomly assigned to one of two groups: 1. Exercise Training Group: Participants will follow a 20-week home-based exercise program, which includes structured exercises designed to improve physical fitness. 2. Mobility and Flexibility Training: Participants in this group will follow a 20-week program focused on mobility and flexibility exercises. The study will collect data through various assessments, including: * Clinical Exams: To monitor physical health and MS-related symptoms. * Brain MRI: To measure changes in brain structure. * Eye Tracking (SickKids participants only): To assess brain activity and cognitive functions. * Cognitive Testing: To evaluate memory, attention, and other cognitive abilities. * Blood Draws: To measure blood biomarkers related to brain health, such as Brain-Derived Neurotrophic Factor (BDNF) and irisin, which are proteins thought to be linked to exercise benefits. * Questionnaires: To gather information on mental health, including levels of depression and overall well-being. * Accelerometry: To measure physical activity levels throughout the study. What the Investigators Hope to Learn: The main goal of this study is to see whether it is practical to run a large-scale trial using a home-based exercise program for youth with MS. The investigators will look at whether it is possible to successfully recruit, retain, and engage participants in the program and how well they adhere to the exercise plan. In addition to feasibility, the study has several exploratory objectives: 1. Mental Health: The investigators want to see if participants in the exercise group show improvements in depressive symptoms compared to the control group. 2. Cognition: The investigators will evaluate whether exercise has a positive effect on thinking skills, such as memory and attention. 3. Brain Health: Through brain MRI scans, the investigators will examine whether exercise protects or enhances brain volume in areas linked to MS. 4. Fitness Levels: The investigators will measure if participants improve their physical fitness as a result of the exercise program. 5. Biomarkers: The investigators will study how exercise impacts blood levels of BDNF and irisin, which may provide insight into the biological mechanisms behind the benefits of exercise. Why It Matters: This study is a critical first step in determining if exercise can be a viable and effective way to improve the lives of youth with MS. If successful, the findings will pave the way for a larger trial that could lead to new, non-medication-based treatments to improve mental health, cognitive function, and overall well-being in young people with MS. By addressing the gaps in understanding how exercise benefits youth with MS, this research could offer valuable insights into developing better care strategies for this population. The results will inform not only how future exercise programs are designed but also provide a deeper understanding of the biological mechanisms linking physical activity to brain health and mood in youth with MS. Study Locations: The study will take place across four sites: * SickKids (Toronto, Canada) * Stollery Children's Hospital (Edmonton, Canada) * Children's Hospital of Philadelphia (Philadelphia, USA) * University of California, San Diego (San Diego, USA) How This Study Will Help in the Future: The information the investigators gather from this feasibility trial will help shape a larger, more definitive study to further explore whether exercise can be widely implemented as a safe and effective treatment option for youth with MS. It could lead to new therapeutic strategies that do not rely solely on medication but focus on holistic approaches to health and wellness.
Interventions
BEHAVIORALExercise Training
The Exercise Training will follow a progressive interval-based training program designed for youth with MS. Participants will engage in three weekly exercise sessions. Participants will be given access to links to live virtual structured exercise sessions. The sessions will be scheduled weekly in partnership with a coach. A trained fitness instructor will lead the participants in a 10-minute warm-up, followed by 30 minutes of interval training, and a 10-minute stretching and cool down activity. Intervals will progress in intensity over the course of the 20-week program and progression will be based on individualized target heart rate zones. The session will be delivered via a live feed in order to foster social support from the participants peers enrolled in the program. Participants will have the option of completing the class in real-time and make up classes will also be available through a repository of sessions accessible through links to the repository cloud.
BEHAVIORALMobility and Flexibility Training
The Mobility and Flexibility Training will be focused on improving mobility and flexibility through three times a week stretching and mobility program. A 5-minute warm up will be followed by a series of stretches and mobility patterns that will be repeated as a circuit four times. Each session will focus on a specific muscle group - upper body, lower body or core. The classes will be led by a fitness instructor in the same manner as the exercise intervention arm with a virtual link sent to the participants.
Sponsors
National Multiple Sclerosis Society
Multiple Sclerosis Society of Canada
University of California, San Diego
Children's Hospital of Philadelphia
Alberta Health Services, Calgary
Queen's University
University of Illinois at Chicago
Unity Health Toronto
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Masking description
To avoid bias or influence in outcomes, participants will not be informed which training group is the intervention group and which is the sham/control group.
Intervention model description
Participants will be randomized at the time of enrolment to either an Exercise Training group or a Mobility and Flexibility Training group.
Eligibility
Sex/Gender
ALL
Age
11 Years to 25 Years
Healthy volunteers
No
Inclusion criteria
* Youth and young adults 11-25 years of age * MS diagnosis or clinically isolated syndrome per revised McDonald diagnostic criteria and International Pediatric MS Study Group Criteria * A score of 10 or above on the CES-DC scale.
Exclusion criteria
* Have non-specific white matter abnormalities and metabolic or infectious etiologies for white matter abnormalities * Do not speak and read English at a level needed to complete the questionnaires (4th grade level) * Have significant motor disability (EDSS ≥4) * Are at increased risk of cardiac or other complications of exercise testing, as determined by the pediatric neurologist or physician
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Participant accrual rate | From enrollment to the end of study | Number of participants enrolled per year |
| Fidelity of delivering the intervention | From enrollment to the end of intervention at 20 weeks | ASPIRE fidelity coaching checklist. This measure assesses the fidelity with which study coaches deliver the intervention during calls with participants. Participants are scored on a scale from 0 to 2, based on the extent to which the intervention components are covered: 0: Did not cover - The intervention component was not addressed during the call. 1. Partially covered - The intervention component was addressed to some extent, but not fully. 2. Fully covered - The intervention component was fully addressed, meeting the intended criteria for delivery. A higher score reflects a more complete and accurate delivery of the intervention as planned. |
| Participant drop-out rate | From enrollment to the end of study | Percentage of total patients that dropped out of study. |
| Adverse event rate | From enrollment to the end of study | Number of adverse events per total participants |
| Completion rate of study measures | From enrollment to the end of study | Percentage of total patients that completed the study measures. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Information Processing Speed - Oral Symbol Digit Test (OSD) | From enrollment to the end of intervention at 20 weeks | The OSD assesses information processing speed, attention, and cognitive efficiency by requiring participants to match numbers with corresponding symbols using a reference key within a 120-seconds time limit. The test is scored based on the total number of correct responses (raw score), with higher scores indicating better performance. Changes in raw scores between Time 1 and Time 2 reflect improvements or declines in cognitive processing speed over time. Normative data are used to compare the participant's performance to age- and education-based averages, providing context for individual scores. |
| Free viewing eye tracking - Saccades | From enrollment to the end of intervention at 20 weeks | This outcome measure evaluates visual attention, cognitive processing, and arousal through key eye-tracking metrics collected during free-viewing tasks. Data are recorded and analyzed to understand participants' visual and cognitive engagement with presented stimuli. The mean saccade rate (MSR) will be calculated as the frequency of macro-saccades (saccades with an amplitude of greater than or equal to 2 degress) across all videos combined. |
| Free viewing eye tracking - Fixations | From enrollment to the end of intervention at 20 weeks | This outcome measure evaluates visual attention, cognitive processing, and arousal through key eye-tracking metrics collected during free-viewing tasks. Data are recorded and analyzed to understand participants' visual and cognitive engagement with presented stimuli.The mean fixation duration (MFD) will be calculated as the average time spent fixating between any two successive saccades across all video clips. |
| PedsQL Core Module | From enrollment to the end of intervention at 20 weeks | This measure evaluates the health-related quality of life (HRQoL) in children and adolescents using the Varni Pediatric Quality of Life Inventory (PedsQL) Core Module. The PedsQL consists of 23 items across four dimensions: Physical, Emotional, Social, and School Functioning. Each item is scored on a 5-point Likert scale, with responses reverse-scored and transformed to a 0-100 scale, where higher scores indicate better HRQoL. |
| Blood myokine irisin measurement | From enrollment to the end of intervention at 20 weeks | Change in blood irisin levels (ng/mL) between baseline and end of 20-week intervention. |
| The Centre for Epidemiological Studies Depression Scale Children's Rating Scale (CES-DC) | From enrollment to the end of intervention at 20 weeks | The Centre for Epidemiological Studies Depression Scale Children's Rating Scale (CES-DC) is a widely used tool for assessing depressive symptoms in children and adolescents. The scale consists of 20 items that measure symptoms of depression experienced during the past week. These symptoms are related to mood, behavior, and physical well-being, and include feelings of sadness, irritability, social withdrawal, and changes in sleep or appetite. Each item is rated on a 4-point Likert scale ranging from 0 (Not At All) to 3 (A Lot). The total score is obtained by summing the ratings across all 20 items, with higher scores indicating more severe depressive symptoms. |
| Screen for Anxiety-Related Disorders (SCARED) | From enrollment to the end of intervention at 20 weeks | The Screen for Anxiety-Related Disorders (SCARED) is a self-report tool designed to screen for anxiety symptoms in children and adolescents. The scale consists of 41 items that assess symptoms related to various anxiety disorders, including generalized anxiety disorder, separation anxiety disorder, social anxiety disorder, and specific phobias. Each item is rated on a 3-point Likert scale: 0 (Not true or hardly ever true), 1 (Somewhat true or sometimes true), and 2 (Very true or often true). The total score is derived by summing the ratings across all items, with higher scores indicating more severe anxiety symptoms. |
| Godin Leisure-Time Exercise Questionnaire (GLTEQ) | From enrollment to the end of intervention at 20 weeks | The GLTEQ is a self-report tool used to assess the frequency and intensity of physical activity during leisure time. The GLTEQ consists of three questions that measure the frequency of strenuous, moderate, and light physical activities performed for at least 15 minutes during a typical week. Participants are asked to report the number of times they engage in each level of activity over the past week, using the following intensity categories: Strenuous activity, Moderate activity, and Light activity. Each question is rated on a 4-point scale: 0 (None), 1 (once a week), 2 (twice a week), and 3 (3 or more times a week). The GLTEQ provides a score by multiplying the frequency of each activity level by a corresponding factor (9 for strenuous, 5 for moderate, and 3 for light), and then summing the results. The final score represents the overall level of physical activity, with higher scores indicating greater levels of leisure-time physical activity. |
| Varni Pediatric Multidimensional Fatigue Scale (PedsQL-MFS) | From enrollment to the end of intervention at 20 weeks | The Varni Pediatric Multidimensional Fatigue Scale (PedsQL-MFS) is a tool designed to measure fatigue in children and adolescents, assessing its impact on daily functioning. The scale includes 18 items across three domains: General Fatigue, Sleep/Rest Fatigue, Cognitive Fatigue. Participants rate their level of fatigue over the past month on a 5-point Likert scale, where higher scores indicate less fatigue. Items are reverse-scored and transformed to a 0-100 scale, with higher scores representing less fatigue. Subscale scores are calculated for each dimension, and a total fatigue score is derived by averaging the scores from all three domains. |
| Blood brain-derived neurotrophic factor (BDNF) measurement | From enrollment to the end of intervention at 20 weeks | Change in blood BDNF levels (ng/mL) between baseline and end of 20-week intervention. |
| Change in brain volumes | From enrollment to the end of intervention at 20 weeks | This outcome measure assesses changes in brain volume following the intervention. MRI scans of the brain will be performed at baseline and at 20 weeks. The outcome metrics include the absolute change in brain volume (mm\^3), percentage change in brain volume, and variance in brain volume changes across participants. |
| Cognitive flexibility - Dimensional Change Card Sort test | From enrollment to the end of intervention at 20 weeks | This outcome measure evaluates cognitive performance based on a combination of accuracy and reaction time. The scoring process combines accuracy and reaction time, using a 2-vector system where each vector is scored from 0 to 5. The final score ranges from 0 to 10. If a participant's accuracy is 80% or lower, the final score is based solely on accuracy. If accuracy exceeds 80%, both accuracy and reaction time are combined to calculate the final score. A score below 4 indicates that accuracy was insufficient (lower than or equal to 80%) to allow for a reaction time score. Higher scores are associated with better cognitive flexibility. Normative data are used to compare the participant's performance to age- and education-based averages, providing a contextual understanding of individual scores. |
| Executive function (Inhibitory control and attention) - Flanker test | From enrollment to the end of intervention at 20 weeks | The scoring method for the Flanker test is identical to that of the DCCS and uses a 2-vector scoring system based on accuracy and reaction time, each scored on a scale from 0 to 5. The final computed score ranges from 0 to 10, representing the participant's overall performance. If a participant's accuracy is 80% or lower, the final computed score is based solely on accuracy. If accuracy exceeds 80%, the reaction time score and accuracy score are combined to calculate the final score. A computed score below 4 indicates that the participant did not achieve sufficient accuracy (lower than or equal to 80%) to include a reaction time component. Higher scores reflect better attention and the ability to ignore distractions, indicating stronger cognitive control. Normative data are used to compare the participant's performance to age- and education-based averages, providing a contextual understanding of individual scores. |
Countries
Canada, United States
Contacts
Primary ContactAnn Yeh, MD
Backup ContactJesse Joynt, MSc
Outcome results
None listed