AUTOREST: Autonomic Function and Cardiovascular Risk in Restless Legs Syndrome

Sponsor

Mauro Manconi (Other)

Overall Status

Completed

CT.gov ID

NCT02025608

Collaborator

University Hospital Inselspital, Berne (Other), Cardiocentro Ticino (Other)

Enrollment

Locations

Arms

Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Restless Legs Syndrome	Drug: Pramipexole Drug: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Other

Official Title:

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

Study Start Date :

Dec 1, 2013

Actual Primary Completion Date :

Dec 31, 2016

Actual Study Completion Date :

Dec 31, 2016

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

Secondary Outcome Measures

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

Other Outcome Measures

Change in chemoreflexes from baseline to 4 weeks [Baseline, Week 4]
Peripheral and central chemoreflex sensitivity derived from carbon dioxide (CO2) rebreathing test

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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 >

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Neurocenter of Southern Switzerland	Lugano	Ticino	Switzerland	6903
2	Department of Neurology, Inselspital	Bern		Switzerland	3010

Sponsors and Collaborators

Mauro Manconi
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