Autonomic Function and Cardiovascular Risk in Restless Legs Syndrome

Autonomic Function and Cardiovascular Risk in Restless Legs Syndrome: AUTOREST, a Case-control Study and a Randomized, Double-blind, Placebo-controlled, Parallel-group, 4-week, Multicenter Study of 0.25mg Pramipexole vs. Placebo in Patients With RLS

The purpose of this study is to explore whether patients with restless legs syndrome (RLS) differ from healthy subjects in daytime and night time autonomic function and cardiovascular risk markers and whether 4 week treatment with pramipexole affects autonomic function and cardiovascular risk markers in patients with RLS.

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.