Exercise Program for Restless Legs Syndrome

(PEARLS Trial)

Overseen By Katie Cederberg, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Disqualifiers: Iron deficiency anemia, Radiculopathy, Diabetes, others

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

Compensation: Varies

Number of Visits: 2

30 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify whether you need to stop taking your current medications, but it requires that participants have untreated restless legs syndrome (RLS). This suggests that you should not be on any current treatment for RLS to participate.

What data supports the effectiveness of the 12-Week RLS Exercise Program treatment for Restless Legs Syndrome?

Research shows that regular exercise can improve symptoms of Restless Legs Syndrome (RLS), with 54% of survey participants reporting that exercise only improves their symptoms. Additionally, a study found that a pain-free walking exercise program reduced RLS symptoms in patients with peripheral artery disease, suggesting exercise can be beneficial for managing RLS. ^{1 2 3 4 5}

Is the Exercise Program for Restless Legs Syndrome safe for humans?

Exercise programs, including those for various conditions, are generally safe for humans. Studies show that while minor injuries like muscle strains can occur, serious problems are rare, especially when starting slowly and gradually increasing intensity. ^{6 7 8 9 10}

How does the 12-Week RLS Exercise Program treatment differ from other treatments for Restless Legs Syndrome?

The 12-Week RLS Exercise Program is unique because it focuses on physical activity as a treatment, which is different from typical drug-based therapies. This program emphasizes exercise to improve physical function and potentially alleviate symptoms, similar to how exercise is used to manage frailty in older adults. ^{11 12 13 14 15}

What is the purpose of this trial?

The goal of this clinical trial is to learn how exercise changes molecules in the blood in people with restless legs syndrome (RLS) to better understand the cause(s) of RLS. The main questions the investigators aim to answer are: How does long-term exercise change proteins in the blood? How does a single exercise session change proteins in the blood? The investigators will compare long-term exercise to no exercise to see if the changes in proteins are specific to exercise. Participants will complete an exercise test and provide blood samples before and after the exercise test. Participants will be randomized (like the flip of a coin) in to either the exercise or no-exercise group for 12 weeks and then complete the exercise test and blood samples again at the end.

Research Team

Emmanuel Mignot, MD

Principal Investigator

Stanford University

Eligibility Criteria

This trial is for adults over 18 with moderate-to-severe untreated Restless Legs Syndrome (RLS) who can walk without assistance. Participants should not be regularly active, defined as engaging in activity for more than two days a week in the past six months.

Inclusion Criteria

I have restless legs syndrome that hasn't been treated yet.

I have moderate-to-severe restless legs syndrome.

I have not been regularly active for the last six months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants complete an exercise test and provide blood samples before and after the exercise test

1 week

1 visit (in-person)

Intervention

Participants are randomized into either the exercise or no-exercise group for 12 weeks

12 weeks

Regular exercise sessions for the exercise group

Follow-up

Participants complete the exercise test and provide blood samples again at the end of the 12-week period

1 week

1 visit (in-person)

Treatment Details

Interventions

• 12-Week RLS Exercise Program

Trial Overview The study tests how a 12-week exercise program affects blood proteins in RLS patients compared to no exercise. It involves an initial exercise test and blood samples, followed by random assignment to either continue exercising or not, then another test and samples after 12 weeks.

Participant Groups

Group I: Exercise Experimental Treatment 1 Intervention

Participants will complete a 12-week, RLS specific exercise program including strength training, cardiovascular exercise, and stretching.

Group II: Non-Exercise Active Control 1 Intervention

Participants will have no intervention or interaction for 12 weeks.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

Findings from Research

A survey of 528 participants with restless legs syndrome revealed that 72% reported positive effects of regular exercise on their symptoms, indicating that exercise can be an effective management strategy for this condition.

Participants noted that maintaining a consistent exercise routine significantly improved their symptoms, while abrupt changes in activity often triggered symptom flare-ups, highlighting the importance of personalized exercise plans for managing restless legs syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Perceptions of exercise and restless legs syndrome: Results from a nationwide survey. Cederberg, KLJ., Sikes, EM., Mignot, E.[2023]

A survey of 513 participants with restless legs syndrome (RLS) revealed that 67% felt a specific exercise program was necessary, and 64% expressed interest in participating, indicating a strong demand for tailored exercise interventions.

Key barriers to participation included accessibility and personal factors, but respondents suggested modifications like individualization of exercises and more home-based options, highlighting the importance of educated exercise providers to enhance program acceptance and effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stakeholder involvement in the optimization of a patient-centered exercise intervention for people with restless legs syndrome. Cederberg, KLJ., Sikes, EM., Mignot, E.[2023]

A 16-week physical activity intervention significantly reduced overall severity of restless legs syndrome (RLS) in adults with multiple sclerosis, with notable improvements during both day and night activities.

The intervention also positively impacted sleep satisfaction and increased total sleep time, suggesting that physical activity may enhance sleep outcomes for individuals with RLS and MS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility and efficacy of a physical activity intervention for managing restless legs syndrome in multiple sclerosis: Results of a pilot randomized controlled trial. Cederberg, KLJ., Motl, RW.[2022]

A pilot trial involving 41 adults with moderate to severe restless legs syndrome (RLS) demonstrated that a 12-week yoga program is feasible and well-accepted, with 73% of participants completing the study and high satisfaction reported in both the yoga and educational film groups.

Participants in the yoga group attended an average of 81% of classes, and all expressed a strong interest in continuing yoga practice, indicating that yoga could be a promising management strategy for RLS in future larger randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Exploratory Randomized Controlled Trial of a 12-Week Yoga Versus Educational Film Program for the Management of Restless Legs Syndrome: Feasibility and Acceptability. Selfe, TK., Montgomery, C., Klatt, M., et al.[2023]

In a study of 286 patients with peripheral artery disease (PAD), 35% were found to have restless leg syndrome (RLS), with a higher prevalence in females, indicating a significant association between RLS and PAD.

A pain-free home-based exercise program led to the disappearance of RLS symptoms in 83% of participants after about 39 days, suggesting that such exercise can improve both sleep quality and mobility, potentially reducing cardiovascular risks in PAD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Restless Leg Syndrome in Peripheral Artery Disease: Prevalence among Patients with Claudication and Benefits from Low-Intensity Exercise. Lamberti, N., López-Soto, PJ., Rodríguez-Borrego, MA., et al.[2020]

In a review of over 5,500 participants from 11 physical activity interventions, no serious study-related adverse events were reported, indicating a high level of safety in these exercise programs.

While minor musculoskeletal injuries were noted, the studies emphasized a 'start low and go slow' approach, suggesting that moderate-intensity physical activity is safe and effective for sedentary, chronically ill, or older populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening, safety, and adverse events in physical activity interventions: collaborative experiences from the behavior change consortium. Ory, M., Resnick, B., Jordan, PJ., et al.[2022]

In a randomized controlled trial involving 209 elderly participants (average age 80), a home-based exercise program was found to be generally safe, with 151 adverse events reported, affecting 47% of participants.

Despite the program's safety, 14% of the adverse events were serious, highlighting that high levels of pre-existing morbidity in this population can pose challenges to maintaining consistent exercise participation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. Hinrichs, T., Bücker, B., Wilm, S., et al.[2015]

The PAR-Q and PARmed-X are important tools for screening individuals before they engage in physical activity, but they need updates to better accommodate people with chronic health conditions and to include individuals of all ages.

Research shows that the risks of being inactive are much greater than the temporary risks associated with exercise, highlighting the need for effective risk stratification and the involvement of qualified exercise professionals in the clearance process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: Consensus Document 2011. Warburton, DE., Gledhill, N., Jamnik, VK., et al.[2022]

A systematic review of 20 studies involving 2018 hospitalized adults with respiratory conditions found that exercise programs, including aerobic and resistance training, were generally well tolerated and had infrequent adverse events, with only seven reported across 7420 training sessions.

The exercise programs varied widely in their design and implementation, with some using objective measures to tailor the initial sessions, highlighting the need for standardized approaches in prescribing exercise for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training for adults hospitalized with an acute respiratory condition: a systematic scoping review. Rice, H., Harrold, M., Fowler, R., et al.[2022]

A systematic review of 773 studies involving over 38,000 participants found that exercise therapy does not increase the risk of serious adverse events, indicating it is a safe intervention.

However, exercise therapy was associated with a higher risk of non-serious adverse events, with a relative risk of 1.19, meaning that for every 6 participants, one additional non-serious adverse event may occur.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis. Niemeijer, A., Lund, H., Stafne, SN., et al.[2022]

A 6-week speed-based exercise program for older adults showed significant improvements in mobility, with a 2-second enhancement in the timed up and go test and a 34% increase in rapid knee extension strength, indicating its efficacy in improving neuromuscular function.

The program not only benefited the lower body but also led to improvements in upper body strength and dexterity, suggesting that speed-based exercises can have widespread neural adaptations even in untrained muscle groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Speed Cycling Intervention Improves Rate-Dependent Mobility in Older Adults. Bellumori, M., Uygur, M., Knight, CA.[2018]

In a study of 31 frail older women participating in a 12-week exercise program, both home-based and center-based programs effectively reversed frailty in 76% of participants, demonstrating significant improvements in muscle strength and physical function.

The home-based program showed high adherence rates, while the center-based program was more effective in reversing frailty status, indicating that both approaches can be beneficial for frail older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does Home-Based Exercise Improve the Physical Function of Prefrail Older Women? Garcia, RNSA., Costa, SN., Garcia, EDSA., et al.[2021]

A video-based exercise program was developed for elderly individuals to help them recover from locomotive syndrome, showing promising results in a pilot study with 20 volunteers.

In a larger study with 120 elderly participants, the video program significantly improved low back pain, single-leg standing time, and 6-meter walking time compared to other teaching methods, indicating its effectiveness for enhancing mobility and reducing pain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of a video exercise program for locomotive syndrome in the elderly. Hashizume, H., Yoshimura, N., Nagata, K., et al.[2019]

Exercise is the most effective therapy to reverse frailty in older adults, with recommendations for pre-frail individuals to engage in 2-3 sessions per week of 45-60 minutes, focusing on aerobic, resistance, flexibility, and balance training.

Frail older adults should exercise 3 times a week for 30-45 minutes, primarily emphasizing aerobic training, with intensity levels set to a 'somewhat hard' effort on the Borg CR10 scale to maximize functional improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise prescription to reverse frailty. Bray, NW., Smart, RR., Jakobi, JM., et al.[2022]

A randomized controlled trial is set to evaluate a 12-week home-based exercise program for patients aged 70 and older, aiming to improve functional lower body strength and overall physical functioning.

The program, delivered through general practitioners and exercise therapists, is based on behavior change strategies and will assess various outcomes, including physical activity levels and health-related quality of life, to determine its effectiveness compared to a control group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of an exercise programme for chronically ill and mobility-restricted elderly with structured support by the general practitioner's practice (HOMEfit) - study protocol of a randomised controlled trial. Hinrichs, T., Moschny, A., Brach, M., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Perceptions of exercise and restless legs syndrome: Results from a nationwide survey. [2023]

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

Stakeholder involvement in the optimization of a patient-centered exercise intervention for people with restless legs syndrome. [2023]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility and efficacy of a physical activity intervention for managing restless legs syndrome in multiple sclerosis: Results of a pilot randomized controlled trial. [2022]

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

An Exploratory Randomized Controlled Trial of a 12-Week Yoga Versus Educational Film Program for the Management of Restless Legs Syndrome: Feasibility and Acceptability. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Restless Leg Syndrome in Peripheral Artery Disease: Prevalence among Patients with Claudication and Benefits from Low-Intensity Exercise. [2020]

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

Screening, safety, and adverse events in physical activity interventions: collaborative experiences from the behavior change consortium. [2022]

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

Adverse events in mobility-limited and chronically ill elderly adults participating in an exercise intervention study supported by general practitioner practices. [2015]

8. Canada pubmed.ncbi.nlm.nih.gov

Evidence-based risk assessment and recommendations for physical activity clearance: Consensus Document 2011. [2022]

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

Exercise training for adults hospitalized with an acute respiratory condition: a systematic scoping review. [2022]

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

Adverse events of exercise therapy in randomised controlled trials: a systematic review and meta-analysis. [2022]

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

High-Speed Cycling Intervention Improves Rate-Dependent Mobility in Older Adults. [2018]

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

Does Home-Based Exercise Improve the Physical Function of Prefrail Older Women? [2021]

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

Development and evaluation of a video exercise program for locomotive syndrome in the elderly. [2019]

14. Canada pubmed.ncbi.nlm.nih.gov

Exercise prescription to reverse frailty. [2022]

15. England pubmed.ncbi.nlm.nih.gov

Effects of an exercise programme for chronically ill and mobility-restricted elderly with structured support by the general practitioner's practice (HOMEfit) - study protocol of a randomised controlled trial. [2023]