Exercise for Multiple Sclerosis

(FIT-ATOMIC Trial)

Recruiting at 3 trial locations

Overseen By Carmen Yea, MSc

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: The Hospital for Sick Children

Disqualifiers: Non-specific white matter, Motor disability, Cardiac risk, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 20 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

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 Intervention group or a Mobility and Flexibility Training control 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, MEG/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.

Will I have to stop taking my current medications?

The trial information does not specify whether participants need to stop taking their current medications. It focuses on exercise as a non-drug approach, so it's best to discuss your current medications with the trial coordinators.

What data supports the effectiveness of the treatment Exercise Training Intervention, Mobility and Flexibility Training for Multiple Sclerosis?

Research shows that exercise training can help people with multiple sclerosis by improving walking, balance, thinking skills, fatigue, mood, and overall quality of life. This suggests that exercise, including mobility and flexibility training, can be a valuable part of managing MS symptoms. ^{1 2 3 4 5}

Is exercise safe for people with multiple sclerosis?

Exercise is generally safe for people with multiple sclerosis. Studies show that exercise does not increase the risk of relapse and the risk of adverse events (unwanted effects) is similar to that in healthy people. ^{6 7 8 9 10}

How is the exercise training intervention treatment for multiple sclerosis different from other treatments?

Exercise training for multiple sclerosis is unique because it is a non-drug approach that can improve physical function and brain health without increasing the risk of relapses. It is generally safe, well-tolerated, and can be tailored to individuals with varying levels of disability, offering benefits even to those with significant mobility challenges. ^{11 12 13 14 15}

Eligibility Criteria

This trial is for young individuals with Multiple Sclerosis. They should be able to perform exercises at home and willing to undergo various assessments, including brain scans and blood tests. Details on specific age or health status requirements are not provided.

Inclusion Criteria

A score of 10 or above on the CES-DC scale.

I am between 11 and 25 years old.

I have been diagnosed with MS or had a single MS-like episode.

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)

Are at increased risk of cardiac or other complications of exercise testing, as determined by the pediatric neurologist or physician

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Initial assessments including clinical exams, brain MRI, MEG/eye tracking, cognitive testing, blood draws, and questionnaires

1 week

1 visit (in-person)

Treatment

Participants engage in a 20-week home-based exercise program or a mobility and flexibility training program

20 weeks

Weekly virtual sessions

Midpoint Assessment

Accelerometry and other assessments to track progress at 10 weeks

1 week

1 visit (virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including final assessments

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Exercise Training Intervention
• Mobility and Flexibility Training

Trial Overview The study is testing a 20-week home-based exercise program against a control group doing mobility and flexibility training. It aims to see if the exercise program can improve physical activity levels, mental health, cognitive function, and biological markers in youth with MS.

Participant Groups

Group I: Exercise Training Intervention Group Active Control 1 Intervention

The exercise training intervention 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 established from baseline exercise testing.

Group II: Control Group Placebo Group 1 Intervention

The Mobility \& Flexibility Training Program is a sham intervention designed to focus on mobility and flexibility. The sham intervention 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.

Who Is Running the Clinical Trial?

The Hospital for Sick Children

Lead Sponsor

Trials

724

Recruited

6,969,000+

Alberta Health Services, Calgary

Collaborator

Trials

15

Recruited

2,600+

Children's Hospital of Philadelphia

Collaborator

Trials

749

Recruited

11,400,000+

University of California, San Diego

Collaborator

Trials

1,215

Recruited

1,593,000+

University of Illinois at Chicago

Collaborator

Trials

653

Recruited

1,574,000+

Unity Health Toronto

Collaborator

Trials

572

Recruited

470,000+

Queen's University

Collaborator

Trials

382

Recruited

122,000+

National Multiple Sclerosis Society

Collaborator

Trials

100

Recruited

10,600+

Multiple Sclerosis Society of Canada

Collaborator

Trials

17

Recruited

990+

Queen's University

Collaborator

Findings from Research

A meta-analysis of 17 randomized controlled trials involving 568 participants with multiple sclerosis (MS) found that exercise training leads to a significant small reduction in fatigue, with an effect size of 0.45.

The results indicate that exercise can be an effective intervention for managing fatigue in individuals with MS, providing a potential strategy for improving their quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis. Pilutti, LA., Greenlee, TA., Motl, RW., et al.[2022]

Exercise training can lead to small but significant improvements in various aspects of life for people with multiple sclerosis (MS), including walking, balance, cognition, fatigue, depression, and overall quality of life.

The review emphasizes the importance of promoting exercise as a key component of clinical care for MS patients, suggesting that healthcare providers, especially neurologists, should actively encourage exercise training based on recent guidelines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits of Exercise Training in Multiple Sclerosis. Motl, RW., Sandroff, BM.[2022]

Over a 2.5-year study involving 269 participants with relapsing-remitting multiple sclerosis, significant improvements were observed in both self-reported and objectively measured physical activity, along with self-efficacy and walking impairment.

Changes in physical activity were strongly associated with improvements in self-efficacy, suggesting that enhancing self-confidence may be key to promoting and maintaining physical activity in individuals with multiple sclerosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Longitudinal change in physical activity and its correlates in relapsing-remitting multiple sclerosis. Motl, RW., McAuley, E., Sandroff, BM.[2022]

A systematic review of 20 randomized controlled trials involving exercise training in individuals with multiple sclerosis showed that exercise significantly improves muscular fitness (small effect size of 0.27) and cardiorespiratory fitness (moderate effect size of 0.47).

The results indicate that while exercise training leads to beneficial changes in fitness levels for people with MS, the improvements in muscular fitness are smaller compared to those in cardiorespiratory fitness, highlighting the importance of exercise in rehabilitation programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis. Platta, ME., Ensari, I., Motl, RW., et al.[2022]

A systematic review of 40 randomized controlled trials involving 1780 participants found that exercise training does not increase the risk of clinical relapse or adverse events in individuals with multiple sclerosis, suggesting it is a safe intervention.

The analysis showed no significant differences in the rates of relapse, adverse events, or serious adverse events between exercise training and non-exercise groups, supporting the promotion of exercise as a beneficial activity for people with MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis. Learmonth, YC., P Herring, M., Russell, DI., et al.[2023]

A systematic review of 26 randomized controlled trials involving 1295 participants found that exercise training in individuals with multiple sclerosis (MS) did not increase the risk of relapse, with a relapse rate of 4.6% for exercise compared to 6.3% for control.

The study also reported that the rate of adverse events (AEs) was similar between exercise (2.0%) and control (1.2%) groups, indicating that exercise training is generally safe and does not pose a higher risk of AEs compared to healthy populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of exercise training in multiple sclerosis: a systematic review. Pilutti, LA., Platta, ME., Motl, RW., et al.[2022]

Exercise has been shown to provide significant benefits for individuals with multiple sclerosis (MS), improving both physical function and quality of life, as supported by recent meta-analyses and literature reviews.

The chapter emphasizes that exercise is safe for people with MS, and it provides guidelines for how to effectively prescribe exercise to maximize these benefits while ensuring safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise and Multiple Sclerosis. Motl, RW.[2020]

Recent studies indicate that exercise training can provide significant benefits for individuals with multiple sclerosis (MS), improving fitness, quality of life, and potentially reducing disability.

The review highlights the possible biological mechanisms behind these benefits, such as the role of neurotrophic factors and anti-inflammatory cytokines, suggesting that exercise may have neuroprotective effects in MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment. Heesen, C., Romberg, A., Gold, S., et al.[2022]

Exercise is an effective behavioral approach for improving function and managing symptoms in individuals with multiple sclerosis (MS), supported by literature reviews and meta-analyses.

The review emphasizes that exercise is generally safe for people with MS, with low reports of relapses and adverse events, and provides guidelines for safe exercise practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefits, safety, and prescription of exercise in persons with multiple sclerosis. Motl, RW.[2022]

Exercise training is now widely recommended for managing multiple sclerosis (MS), reflecting over 25 years of research supporting its benefits for individuals with the condition.

The paper highlights eight emerging research areas, such as behavior change interventions and telerehabilitation, that could enhance the effectiveness and implementation of exercise in clinical practice for MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current perspectives on exercise training in the management of multiple sclerosis. Motl, RW., Sandroff, BM.[2021]

Exercise is a safe and well-tolerated intervention that can effectively improve modifiable impairments in individuals with multiple sclerosis (MS).

Properly prescribed exercise programs, following general guidelines, can enhance the management of MS, particularly for those with more severe symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise in multiple sclerosis. Sandoval, AE.[2022]

Exercise therapy is a safe and effective nonpharmacological treatment for people with multiple sclerosis (MS), showing improvements in physical function without increasing the risk of relapses.

In addition to enhancing physical capabilities, exercise therapy positively impacts brain health, leading to improvements in brain volume and cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise therapy in multiple sclerosis and its effects on function and the brain. Dalgas, U.[2018]

A systematic review of 19 studies found that exercise training, particularly adapted modalities like body-weight support treadmill training and electrical stimulation cycling, can lead to significant improvements in mobility, physical fitness, and quality of life for individuals with severe mobility impairment due to multiple sclerosis (MS).

While conventional exercise training showed some benefits, the majority of positive outcomes were associated with adapted exercise approaches, highlighting the need for accessible exercise interventions for people with MS who have high levels of disability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions. Edwards, T., Pilutti, LA.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Effects of exercise training on fatigue in multiple sclerosis: a meta-analysis. [2022]

2. England pubmed.ncbi.nlm.nih.gov

The MoXFo Initiative: Using consensus methodology to move forward towards internationally shared vocabulary in multiple sclerosis exercise research. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Benefits of Exercise Training in Multiple Sclerosis. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Longitudinal change in physical activity and its correlates in relapsing-remitting multiple sclerosis. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Effect of Exercise Training on Fitness in Multiple Sclerosis: A Meta-Analysis. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety of exercise training in multiple sclerosis: An updated systematic review and meta-analysis. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

The safety of exercise training in multiple sclerosis: a systematic review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Exercise and Multiple Sclerosis. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Physical exercise in multiple sclerosis: supportive care or a putative disease-modifying treatment. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Benefits, safety, and prescription of exercise in persons with multiple sclerosis. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Current perspectives on exercise training in the management of multiple sclerosis. [2021]

12. United States pubmed.ncbi.nlm.nih.gov

Exercise in multiple sclerosis. [2022]

13. England pubmed.ncbi.nlm.nih.gov

Exercise therapy in multiple sclerosis and its effects on function and the brain. [2018]

14. Netherlands pubmed.ncbi.nlm.nih.gov

The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions. [2022]

15. Italy pubmed.ncbi.nlm.nih.gov

High-intensity interval training combined with resistance training improves physiological capacities, strength and quality of life in multiple sclerosis patients: a pilot study. [2022]