Analysis of Sympathetic Activity in Willis-Ekbom Disease (MIBG-RLS)

September 26, 2025 updated by: University Hospital, Montpellier

Willis-Ekbom disease (WED), also known as restless legs syndrome (RLS) is a common neurological sensorimotor disorder that typically impairs sleep and quality of life, likely consequent to a central dopaminergic dysfunction associated to brain iron deficiency. Periodic limb movements (PLMS) in sleep are present in 80% of patients with WED. PLMS are often associated with micro-arousals that contribute to sleep fragmentation and repeated increases of blood pressure and heart rate throughout the night, thus representing an increased risk for hypertension and cardiovascular diseases (CVD).

Willis-Ekbom disease affects people with higher cardiovascular risk factors, such as advanced age, obesity, diabetes mellitus and hypercholesterolemia. However, previous observational, cross-sectional or longitudinal population-based studies on the association between RLS and CVD and hypertension showed controversial results.

While the pathophysiology of RLS is yet to be elucidated and is likely multifactorial, one theory involves a reduction in dopaminergic outflow to the preganglionic sympathetic neurons in the dorsal horn of the spinal cord. Dopamine inhibits preganglionic sympathetic neurons, therefore a reduction in dopamine may in turn increase sympathetic outflow.

Based on this notion, the investigators hypothesize an increase of sympathetic autonomic activity in Willis-Ekbom disease responsible for the recurrent increase in blood pressure and heart rate during sleep, which may play a role in increasing the risk of cardiovascular diseases.

The aim of this study is to analyze the autonomic nervous activity in patients with WED compared to healthy volunteers controls. The investigators will measure primarily the cardiac sympathetic activity by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy and secondarily the sympathetic nerve activity by the plasmatic pro inflammatory biomarkers and urinary catecholamine levels and the circadian variation of blood pressure and heart rate as assessed by the 24-hour ambulatory blood pressure monitoring.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 74 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Non-specific inclusion criteria (CASE + CONTROL)

    • 18 years-old or more, and less than 75 years-old
    • French-speaking
    • able to understand the study
    • signed written informed consent
    • affiliated to social security

  • CASE-specific inclusion criteria

    • 5 " International RLS Study Group (IRLSSG) 2012 " positive criteria
    • RLS severity scale (IRLS) score ≥ 15
    • ferritin > 50 ng/ml
    • periodic limb movements index > 10/hour
    • idiopathic (or primary) Willis-Ekbom disease not treated with dopaminergic agonists or pregabalin or gabapentin in the last 8 days, at least 3 years of disease duration with symptoms recurring at least 3 times a week

Exclusion Criteria:

  • Non-specific exclusion criteria (CASE + CONTROL)

    • vulnerable subject : subject deprived of liberty or protected by law (trusteeship, legal guardianship), pregnant or breastfeeding woman
    • exclusion period after other research protocol
    • malignant neoplastic disease treated in the last 12 months
    • medical history of cardiovascular disease (ischemic heart disease, heart failure, stroke, hypertension, sleep apnea syndrome)
    • antidepressant, neuroleptic, sympathomimetic, sympatholytic, vasculotropic, dopamine agonists, opiate treatments

  • CASE-specific exclusion criteria

    - restless legs syndrome secondary to renal failure, hemochromatosis, neurologic disorders, iatrogenesis

  • CONTROL-specific exclusion criteria - Willis-Ekbom Disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Willis-Ekbom disease patients (CASE)
Other: Sympathetic nervous activity measurement
Polysomnography, MIBG myocardic scintigraphy, and 24h blood pressure measurement
Experimental: Healthy volunteers (CONTROL)
Other: Sympathetic nervous activity measurement
Polysomnography, MIBG myocardic scintigraphy, and 24h blood pressure measurement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG uptake based on the ratio heart/mediastinum
Time Frame: Day 0
Day 0

Secondary Outcome Measures

Outcome Measure
Time Frame
Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG washout.
Time Frame: Day 0
Day 0
Analysis of circadian variations of blood pressure and heart rate assessed by the 24-hour ambulatory blood pressure monitoring
Time Frame: Day 0
Day 0
Measurement of pro inflammatory biomarkers and urinary catecholamines levels
Time Frame: Day 0
Day 0
5) Analysis of mean increases of blood pressure and heart rate based on sleep stages, micro-arousals, periodic limb movements and sleep apnoeas as measured by continuous non-invasive blood pressure monitoring
Time Frame: Day 0
Day 0

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Montpellier

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2017

Primary Completion (Estimated)

October 5, 2027

Study Completion (Estimated)

October 5, 2027

Study Registration Dates

First Submitted

October 7, 2016

First Submitted That Met QC Criteria

October 7, 2016

First Posted (Estimated)

October 11, 2016

Study Record Updates

Last Update Posted (Estimated)

October 2, 2025

Last Update Submitted That Met QC Criteria

September 26, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RECHMPL16_0056

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Subscribe