search
Back to results

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

Primary Purpose

Willis-Ekbom Disease, Restless Legs Syndrome

Status
Unknown status
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Sympathetic nervous activity measurement
Sponsored by
University Hospital, Montpellier
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Willis-Ekbom Disease

Eligibility Criteria

18 Years - 74 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • University Hospital of MontpellierRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Willis-Ekbom disease patients (CASE)

Healthy volunteers (CONTROL)

Arm Description

Outcomes

Primary Outcome Measures

Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG uptake based on the ratio heart/mediastinum

Secondary Outcome Measures

Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG washout.
Analysis of circadian variations of blood pressure and heart rate assessed by the 24-hour ambulatory blood pressure monitoring
Measurement of pro inflammatory biomarkers and urinary catecholamines levels
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

Full Information

First Posted
October 7, 2016
Last Updated
September 10, 2020
Sponsor
University Hospital, Montpellier
search

1. Study Identification

Unique Protocol Identification Number
NCT02929732
Brief Title
Analysis of Sympathetic Activity in Willis-Ekbom Disease
Acronym
MIBG-RLS
Official Title
Analysis of Sympathetic Activity in Willis-Ekbom Disease
Study Type
Interventional

2. Study Status

Record Verification Date
September 2020
Overall Recruitment Status
Unknown status
Study Start Date
March 21, 2017 (Actual)
Primary Completion Date
March 2022 (Anticipated)
Study Completion Date
March 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Montpellier

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Willis-Ekbom Disease, Restless Legs Syndrome

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Willis-Ekbom disease patients (CASE)
Arm Type
Experimental
Arm Title
Healthy volunteers (CONTROL)
Arm Type
Experimental
Intervention Type
Other
Intervention Name(s)
Sympathetic nervous activity measurement
Intervention Description
Polysomnography, MIBG myocardic scintigraphy, and 24h blood pressure measurement
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG washout.
Time Frame
Day 0
Title
Analysis of circadian variations of blood pressure and heart rate assessed by the 24-hour ambulatory blood pressure monitoring
Time Frame
Day 0
Title
Measurement of pro inflammatory biomarkers and urinary catecholamines levels
Time Frame
Day 0
Title
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
74 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Facility Information:
Facility Name
University Hospital of Montpellier
City
Montpellier
ZIP/Postal Code
34295
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yves Dauvilliers, PhD
Phone
+33467336361
Email
y-dauvilliers@chu-montpellier.fr

12. IPD Sharing Statement

Learn more about this trial

Analysis of Sympathetic Activity in Willis-Ekbom Disease

We'll reach out to this number within 24 hrs