Autonomic Function and Cardiovascular Risk in Restless Legs Syndrome

Inclusion criteria

(all participants):

• Willingness to participate and written informed consent
• Aged 30 to 65 years at the time of screening
• Body mass index (BMI) ≤ 30
• Unremarkable neurological and physical examination
• Unremarkable standard blood parameter according to local reference values

Additional Inclusion Criteria for Restless Legs Syndrome (RLS) Patients:

• RLS according to current standard international criteria
• RLS symptoms ≥ 2 times per week for ≥ 1 year and during the past 12 months.
• Either current international RLS severity scale (IRLS) ≥ 15 or current IRLS ≥ 10 and RLS symptoms ≥ 4 times per week during the past 3 months.

Exclusion criteria

(all participants):

• Pregnancy, or breast feeding at time of screening.
• Recent anaesthesia (last 3 months).
• Sleep related breathing disorders during nocturnal polysomnography:
• Current history of psychiatric disorders according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV).
• Life time history of any diagnosis of, medication or intervention for cardiovascular diseases.
• Current chronic treatment that may affect autonomic function.
• Any significant neurological disease or diagnosed metabolic diseases that may affect cardiovascular function and/or increase cardiovascular risk.
• Any unstable medical condition.
• Smoking > 5 cigarettes per day during the last 2 years.
• Work involving night shifts (22:00 - 06:00 h) during the past 2 years.
• Travel with > 6 time zone differences during the past 6 months.
• Participation in any other study involving investigational or marketed products concomitantly or within 3 months prior to the screening visit.
• Current participation in other clinical trials.

Additional Exclusion Criteria for RLS Patients

• Exposure to dopaminergic drugs > 12 months during life time and/or > 1 week during the past 3 months and/or current or during the past month.
• Exposure to other RLS relevant medication (such as opioids, antiepileptics, clonidine except hypnotics such as benzodiazepines) > 24 months during life time and/or > 1 week during the past 3 months and/or current intake.
• Intake of hypnotics (such as benzodiazepines) during the past month.
• Other significant sleep disorder except symptoms potentially related to RLS such as insomnia and daytime sleepiness.
• Any contraindication or known hypersensitivity to dopaminergic drugs.

Additional Exclusion Criteria for Control Subjects

• Any pharmacological treatment that may affect sleep and/or sleep related movement disorders during the last 3 months.
• Any clinically significant sleep disorders according to the International Classification of Sleep Disorders (ICSD)12.
• Increased daytime sleepiness as indicated by an Epworth Sleepiness Scale (ESS) score > 11.