MIBG-RLS: Analysis of Sympathetic Activity in Willis-Ekbom Disease

• Sponsor: University Hospital, Montpellier (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT02929732
• Collaborator: (none)
• Enrollment: 40
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 59.3
• Patients Per Site Per Month: 0.7

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Willis-Ekbom Disease; Restless Legs Syndrome	Other: Sympathetic nervous activity measurement	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 40 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Analysis of Sympathetic Activity in Willis-Ekbom Disease
• Actual Study Start Date: Mar 21, 2017
• Anticipated Primary Completion Date: Mar 1, 2022
• Anticipated Study Completion Date: Mar 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG uptake based on the ratio heart/mediastinum [Day 0]

Secondary Outcome Measures

1. Cardiac sympathetic activity measurement by the 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy. Analysis of 123I-MIBG washout. [Day 0]

2. Analysis of circadian variations of blood pressure and heart rate assessed by the 24-hour ambulatory blood pressure monitoring [Day 0]

3. Measurement of pro inflammatory biomarkers and urinary catecholamines levels [Day 0]

4. 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 [Day 0]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 74 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospital of Montpellier	Montpellier		France	34295

Sponsors and Collaborators

• University Hospital, Montpellier

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University Hospital, Montpellier
• ClinicalTrials.gov Identifier: NCT02929732
• Other Study ID Numbers: 9689
• First Posted: Oct 11, 2016
• Last Update Posted: Sep 11, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Restless Legs Syndrome

Study Results

No Results Posted as of Sep 11, 2020