Autonomic Function and Cardiovascular Risk in Restless Legs Syndrome (AUTOREST)

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.

Study Overview

• Status: Completed
• Conditions: Restless Legs Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: Pramipexole

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • Department of Neurology, Inselspital
  • Ticino
    • Lugano, Ticino, Switzerland, 6903
      • Neurocenter of Southern Switzerland

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pramipexole; Pramipexole, 0.25 mg, daily for 4 weeks	Drug: Pramipexole
Placebo Comparator: Placebo; Placebo, daily for 4 weeks	Drug: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in heart rate activations during sleep from baseline to 4 weeks	Number and amplitude of periodic leg movements during sleep (PLMS) and non-PLMS related heart rate activations during stable nocturnal sleep	Baseline, Week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in baroreflex from baseline to 4 weeks	Baroreflex sensitivity and baroreflex gain derived from tilt table tes	Baseline, Week 4
Change in blood serum markers from baseline to 4 weeks	Highly-sensitive C reactive protein (hsCRP), lipoprotein-associated phospholipase A2 (lP-PLA2), and oxidised low density lipoprotein (oxLDL)	Baseline, Week 4

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in chemoreflexes from baseline to 4 weeks	Peripheral and central chemoreflex sensitivity derived from carbon dioxide (CO2) rebreathing test	Baseline, Week 4

Collaborators and Investigators

• Sponsor: Mauro Manconi
• Collaborators: University Hospital Inselspital, Berne; Cardiocentro Ticino
• Investigators: Principal Investigator: Mauro Manconi, PhD, MD, Neurocenter of Southern Switzerland; Principal Investigator: Claudio L.A. Bassetti, MD, Department of Neurology, Inselspital

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): December 31, 2016
• Study Completion (Actual): December 31, 2016

Study Registration Dates

• First Submitted: December 23, 2013
• First Submitted That Met QC Criteria: December 30, 2013
• First Posted (Estimate): January 1, 2014

Study Record Updates

• Last Update Posted (Estimate): January 24, 2017
• Last Update Submitted That Met QC Criteria: January 23, 2017
• Last Verified: January 1, 2017

More Information

Terms related to this study

• Keywords: Restless legs syndrome
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Neurologic Manifestations; Neurobehavioral Manifestations; Disease; Dyskinesias; Psychomotor Disorders; Parasomnias; Syndrome; Psychomotor Agitation; Restless Legs Syndrome; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Protective Agents; Dopamine Agonists; Dopamine Agents; Antioxidants; Antiparkinson Agents; Anti-Dyskinesia Agents; Pramipexole
• Other Study ID Numbers: NSI.13.01; 320030_144007 (Other Grant/Funding Number: Swiss National Science Foundation)