EXPLORATORY STUDY OF THE POTENTIAL OF THERAPEUTIC EXERCISE IN THE TREATMENT OF WILLIS-EKBOM DISEASE

Estudio Exploratorio Del Potencial Del Ejercicio Terapeútico en el Tratamiento de la Enfermedad de Willis-Ekbom

The goal of this clinical trial is to learn whether a home-based therapeutic exercise program can improve symptoms of restless legs syndrome (RLS), also known as Willis-Ekbom disease, in adults with chronic RLS. It will also assess whether the program affects daytime sleepiness and quality of life, and whether participants can follow and tolerate the exercises.

The main questions it aims to answer are:

• Does a myofascial self-stretching routine improve RLS symptoms?
• Does the exercise program affect daytime sleepiness and quality of life?

Researchers will compare two low-risk home exercise routines: a myofascial self-stretching program based on Mézières and Global Active Stretching principles and Buerger-Allen exercises. Participants will be assigned to one of two exercise sequences and will complete their routine over 2 weeks.

Participants will:

• complete a clinical assessment at the start and end of the study;
• perform a 10- to 20-minute exercise session at home each night, preferably before bedtime;
• record their RLS symptoms each day; and
• keep their usual RLS medication stable during the study.

Restless legs syndrome (RLS), also known as Willis-Ekbom disease, is a neurological disorder characterized by an urge to move the legs, usually accompanied by unpleasant sensations that begin or worsen during rest and are more prominent in the evening or at night. Pharmacological treatments are available, but some people have an insufficient response, experience adverse effects, or develop worsening of symptoms over time. This exploratory study evaluates a non-pharmacological and non-invasive home-based exercise approach intended to provide preliminary evidence for future studies.

The investigational exercise program consists of self-administered myofascial stretching derived from the Mézières therapeutic approach and Global Active Stretching. The exercises combine sustained low-load muscle activity, low-intensity stretching, controlled breathing with emphasis on expiration, and focused attention to posture and movement. The comparator is a Buerger-Allen exercise routine based mainly on lower-limb positioning and ankle movements. No investigational drug or medical device is used.

The study uses a randomized, two-sequence design. Participants complete 2 weeks of home-based exercise. One group of participants performs the myofascial self-stretching routine and the other group completes the Buerger-Allen exercise routine. Allocation is intended to maintain comparable groups with respect to relevant participant characteristics. Participants are not told which routine is hypothesized to have a greater effect on RLS symptoms, and the evaluating research team is blinded to group assignment. Participants are also asked not to discuss their assigned exercise routines with other participants.

Participants are recruited from volunteers linked to the Spanish Restless Legs Syndrome Association (Asociación Española de Piernas Inquietas, AESPI). Clinical eligibility and the diagnosis of RLS are confirmed by a neurologist. Exercise instructions are provided before the intervention, with the possibility of in-person or remote participation for people living outside the Madrid region. Participants receive detailed instructional material, including videos and written guidance, and perform the exercises independently at home, preferably shortly before bedtime. Usual RLS medication is kept stable during the study unless a treating physician determines that a change is clinically necessary.

Clinical assessments are performed at the beginning and end of the study using validated measures of RLS symptom severity, daytime sleepiness, and health-related quality of life. Participants also record symptom intensity daily and may report comments about sleep, discomfort, symptoms, or difficulties with the exercises. Baseline information includes relevant clinical and lifestyle variables and recent laboratory measures related to iron metabolism. AESPI collects participant-reported information and provides pseudonymized data to the research team.

The analysis is exploratory. Quantitative variables will be summarized using means and standard deviations or medians and interquartile ranges, as appropriate, and categorical variables using frequencies and percentages. Changes over time will be evaluated using paired statistical tests, with non-parametric methods used when appropriate for the sample size and data distribution. Associations between variables will be explored using correlation analyses. Statistical significance will be assessed using a two-sided threshold of p < 0.05.

The study is intended to explore the therapeutic potential, tolerability, and feasibility of a simple home-based exercise program. It is not designed to replace established RLS treatments or to provide definitive evidence of clinical efficacy.

Inclusion Criteria:

• Age ≥18 years.
• Resident in Spain, preferably in or near the Community of Madrid.
• Clinical diagnosis of restless legs syndrome (RLS) according to the 2014 International Restless Legs Syndrome Study Group (IRLSSG) diagnostic criteria, confirmed through clinical assessment by a neurologist.
• Symptoms predominantly affecting the legs.
• Under medical follow-up for at least 3 months before enrollment, regardless of current treatment or response to medication.
• If receiving pharmacological treatment for RLS, treatment must have remained stable for at least 1 month before enrollment and must remain stable throughout the study.

Exclusion Criteria:

• Acute or chronic musculoskeletal conditions, such as symptomatic disc herniation, radiculopathy, severe tendinopathy, recent muscle injury, or advanced osteoarthritis, that limit or contraindicate prolonged stretching exercises.
• Severe uncontrolled pain in the lumbar region, pelvis, or lower extremities that prevents completion of the stretching positions required by the protocol.
• Initiation, concurrently with this study, of another non-pharmacological therapy for RLS, such as vibration or compression devices, yoga, or dietary supplements.
• Epilepsy or any other concomitant neurological or neuromuscular disease affecting muscle tone, strength, or postural control that could interfere with the study.
• Pharmacological treatment requiring frequent adjustments that would prevent treatment stability during the study.
• Significant functional limitations, including balance problems, reduced mobility, inability to perform exercises on the floor, or inability to maintain prolonged positions, that prevent correct performance of the exercise protocol.
• Insomnia unrelated to RLS.
• Pregnancy or breastfeeding.