Exercise Training for Depression in Multiple Sclerosis

(METS in MS Trial)

Overseen By Robert W Motl, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Illinois at Chicago

Disqualifiers: Severe mental illness, Ambulatory disability, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

146 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how two different exercise programs can help manage depression and other health issues in people with multiple sclerosis (MS). Participants will follow either a flexibility-focused routine (FLEX-MS, also known as the Stretching Program) or a more intense exercise plan (POWER-MS, also known as the Exercise Training Program) that includes aerobic and strength training. It targets individuals with MS who also have major depressive disorder (MDD) and experience depression's negative impact on daily life. Participants need internet access for remote coaching and should not have experienced an MS relapse or taken steroids in the past month. As an unphased trial, this study provides a unique opportunity to contribute to understanding how exercise can improve mental and physical health in MS patients.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Studies on exercise programs for people with multiple sclerosis (MS) have found that exercising is safe. For both the FLEX-MS and POWER-MS programs, researchers observed no increased risk of worsening MS symptoms or serious side effects compared to not exercising.

FLEX-MS focuses on improving flexibility. Research has shown that these exercises can safely enhance mobility in people with MS without causing harm. Participants generally handled the exercises well.

Similarly, studies on POWER-MS, which includes aerobic and strength training, demonstrated that these exercises are generally safe and do not increase the risk of MS symptoms worsening.

Overall, evidence suggests that both exercise programs are safe and well-tolerated for people with MS. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about these treatments for depression in multiple sclerosis because they offer unique exercise-based approaches, which are not standard in current care. FLEX-MS focuses on enhancing flexibility, emphasizing its role in overall fitness, which is a novel angle compared to traditional medication or psychotherapy. POWER-MS uses a telerehabilitation model to deliver a comprehensive exercise program, combining aerobic and strength training, making it accessible and manageable for individuals with MS. Unlike standard treatments that often involve medication, these approaches harness physical activity to potentially improve mental health and quality of life.

What evidence suggests that this trial's exercise regimens could be effective for managing depression in multiple sclerosis?

Studies have shown that exercise can help reduce depression in people with multiple sclerosis (MS). Research indicates that both stretching and strength exercises can improve mood and quality of life. In this trial, participants may join the FLEX-MS program, where evidence suggests that guided home exercise is more effective than no exercise. Alternatively, participants may join the POWER-MS program, which includes moderate aerobic exercise and strength training, and has been shown to help stabilize mood. Following exercise guidelines can significantly improve depression, making exercise a strong non-drug option for managing depression in MS. ^{6 7 8 9 10}

Who Is on the Research Team?

Robert Motl, Ph.D

Principal Investigator

University of Illinois Chicago

Are You a Good Fit for This Trial?

This trial is for people aged 18-64 with Multiple Sclerosis (MS) and Major Depressive Disorder (MDD), who have internet access, speak English, and are willing to participate in exercise testing. They must not have had a relapse or taken steroids recently, should be relatively inactive based on specific questionnaires, and cannot have certain severe mental illnesses.

Inclusion Criteria

Have you had a relapse in the last 30 days?

Have you ever been diagnosed with depression or had episodes of depression in your past?

Do you exercise 3 times a week or more?

Exclusion Criteria

Do you have a heart condition or bone and joint issue that would prevent you from exercising on a regular basis?

Are you able to walk without the use of a cane, walker, or wheelchair most of the time?

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in either the POWER-MS or FLEX-MS exercise program to manage depression and improve health indicators

16 weeks

Remote coaching sessions

Immediate Follow-up

Assessment of exercise behavior, quality of life, physical activity, muscle strength, aerobic capacity, cognitive performance, depression severity, and fatigue severity

4 weeks

In-person and virtual assessments

Long-term Follow-up

Continued monitoring of exercise behavior, quality of life, physical activity, muscle strength, aerobic capacity, cognitive performance, depression severity, and fatigue severity

16 weeks

In-person and virtual assessments

What Are the Treatments Tested in This Trial?

Interventions

• FLEX-MS
• POWER-MS

Trial Overview The study compares two exercise programs for reducing depression in MS patients: POWER-MS (an exercise training program) versus FLEX-MS (a stretching program). It aims to see which one better decreases the severity of depression immediately and over time.

How Is the Trial Designed?

Group I: POWER-MS Experimental Treatment 1 Intervention

The POWER-MS condition will deliver the Guidelines for Exercise in MS (GEMS) program with a remotely coached/guided, home-based setting using telerehabilitation. GEMS recommends 30 minutes of moderate intensity aerobic activity, 3x/week AND strength training exercises for major muscle groups, 3x/week.

Group II: FLEX-MS Active Control 1 Intervention

The FLEX-MS condition will primarily focus on flexibility as the applicable exercise modality. As such, the program will emphasize that flexibility is an important component of fitness. The goal would be for each participant to enhance their flexibility by engaging in a titrated exercise prescription where the number of sets and time to hold per set will increase throughout the 16-week program.

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

Congressionally Directed Medical Research Programs

Collaborator

Trials

59

Recruited

10,600+

Published Research Related to This Trial

An eight-week progressive resistance training program significantly improved lower extremity strength in multiple sclerosis (MS) patients, with notable increases in knee extension (7.4%) and plantarflexion strength (52%).

Participants also experienced improved walking performance (8.7% increase in stepping) and a reduction in self-reported fatigue, indicating that resistance training can enhance mobility and decrease fatigue in MS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance training improves strength and functional capacity in persons with multiple sclerosis. White, LJ., McCoy, SC., Castellano, V., et al.[2022]

A meta-analysis of 13 randomized controlled trials involving exercise training showed a small but statistically significant improvement in depressive symptoms among people with multiple sclerosis, with an effect size of 0.36.

This suggests that incorporating exercise training can be a beneficial intervention for reducing depression in individuals with MS, despite the overall effect being modest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training improves depressive symptoms in people with multiple sclerosis: results of a meta-analysis. Ensari, I., Motl, RW., Pilutti, LA.[2022]

Maximal strength training (MST) significantly reduced perceived fatigue by nearly 60% and improved functional mobility in people with multiple sclerosis (pwMS) over an 8-week period, indicating its efficacy as a therapeutic intervention.

However, the benefits of MST diminished after a 10-week detraining period, highlighting the need for ongoing training to maintain improvements in strength and mobility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Maximal Strength Training on Perceived-Fatigue and Functional Mobility in Persons with Relapsing-Remitting Multiple Sclerosis. Gomez-Illan, R., Reina, R., Barbado, D., et al.[2021]

In a 12-week randomized controlled trial involving 31 moderately disabled multiple sclerosis patients, progressive resistance training significantly reduced fatigue and improved mood and quality of life compared to a control group.

The positive effects on fatigue, mood, and quality of life were not only significant during the training but were also maintained for at least 12 weeks after the intervention ended.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue, mood and quality of life improve in MS patients after progressive resistance training. Dalgas, U., Stenager, E., Jakobsen, J., et al.[2022]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11468659/

Best practice exercise for emerging depression in multiple ... Exercise training improves depressive symptoms in people with multiple sclerosis: results of a meta-analysis. J Psychosom Res 2014; 76: 465–471. [DOI] ...

2. withpower.com withpower.com/trial/phase-multiple-sclerosis-9-2021-ac349

Exercise Training for Depression in Multiple Sclerosis FLEX-MS and POWER-MS are unique because they focus on exercise training, which has been shown to improve depressive symptoms, fatigue, and quality of life in ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02297932

Physical Activity in Multiple Sclerosis (MS): A Novel ... To date, the evidence suggests that exercise intervention in MS holds anywhere from minimal to great promise depending on the outcome of interest. For some ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2211034823005680

Efficacy of remote exercise and physiotherapy programs on ... Remote exercise and physiotherapy programs are significantly more effective than control group interventions for the management of depression in people with MS.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12039312/

Remotely-delivered exercise training program for improving ... A 16-week theory-based, remotely-delivered, exercise training program for improving cognitive and physical functions in older adults with MS.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6915647/

Exercise Interventions for Improving Flexibility in People with ... Conclusions: There is preliminary evidence from individual studies which indicates that people with MS can improve their lower limb flexibility following ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10637110/

Safety of exercise training in multiple sclerosis - PubMed Central In studies that reported safety outcomes, there was no higher risk of relapse, AE, adverse effects or SAE for exercise training than the comparator.

8. sciencedirect.com sciencedirect.com/science/article/pii/S1551714424002192

Protocol for an NIH stage-I randomized controlled trial The program was safe and had initial feasibility with a compliance rate (71%) for exercise training, moderate increase in self-reported PA (d = 0.57), and ...

9. ijmsc.org ijmsc.org/view/safety-feasibility-and-efficacy-of-an-eccentric-exercise-intervention-in-people-with-multiple-sclerosis-with-ankle-contractures

Safety, Feasibility, and Efficacy of an Eccentric Exercise ... There were no adverse events during or after the eccentric exercise training. There was a 100% adherence rate. All participants enjoyed the ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT07118514

Effect of Resistance Training on Psychophysiological ... This randomized controlled trial investigates the effects of a 20-week progressive resistance training program on psychophysiological parameters in individuals ...