Functional Connectivity of the Interoceptive Network in RLS (IntoRLS)

September 16, 2025 updated by: University Hospital, Bordeaux

Functional Connectivity of the Interoceptive Network in Restless Legs Syndrome (RLS) : an Anatomical-clinical Prospective Study Based on Daily-life Assessment

Restless Legs Syndrome (RLS) is a sensorimotor disorder primarily characterized by an irresistible urge to move the legs while at rest. A key hypothesis suggests that RLS symptoms are linked to abnormal brain function in processing internally generated stimuli, particularly interoception. This distorted perception of the internal bodily state leads to maladaptive behaviors, which may manifest across a wide range of medical and psychiatric disorders. Here, the investigators hypothesize that dysfunction in the insular cortex (IC) may result in a failure of behavioral adaptation, primarily expressed as an urge to move the legs and hyperarousal, even when the body and mind need rest. This project aims to assess the relationship between interoceptive abilities and diurnal fluctuations in IC functional connectivity (FC) in patients with RLS compared to healthy controls. The investigators will also examine correlations between the FC of the interoceptive network, measured in the morning and evening on the same day, using multilayer network analysis, daily fluctuations in RLS symptom severity, and objective measurements of the sleep/wake cycle, gathered through a two-week ambulatory assessment using mobile technologies such as Ecological Momentary Assessment (EMA) and actigraphy, along with scores from self-reported questionnaires. The findings may provide strong evidence to support or refute the hypothesis of interoceptive dysfunction in RLS patients.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Despite extensive research into the pathophysiology of RLS, no unified mechanism has been identified to explain the prominent clinical features of the disorder, including both sensorimotor and non-motor symptoms. One plausible hypothesis is that RLS symptoms are related to abnormal brain function in processing internally generated stimuli, particularly interoception. Distorted perceptions of the internal bodily state can lead to maladaptive behaviors, which may manifest in a wide range of medical disorders, including RLS, attention-deficit/hyperactivity disorder (ADHD), insomnia, eating disorders/obesity, fibromyalgia, and psychiatric conditions. The interoceptive abilities of RLS patients, specifically their capacity to perceive and assess their internal bodily state, have not been extensively studied, despite their potential to deepen our understanding of the sensorimotor discomfort in the legs and associated non-motor symptoms. The IntoRLS project will therefore precisely characterize the temporal variation in symptom severity and interoceptive awareness in RLS patients, alongside their sleep/wake cycle disturbances, using ambulatory assessments. This ecological assessment will be linked to time-of-day variations in intrinsic insular connectivity, assessed via functional brain imaging. At the inclusion visit, eligible participants (both patients and matched controls) will be provided with a study-dedicated smartphone for a two-week period, as well as a wearable actigraph to monitor their activity/rest cycles. Participants will complete self-reported questionnaires assessing the severity of RLS symptoms, ADHD symptoms, anxiety and depression, daytime sleepiness, and arousal predisposition. At the end of the participation period (J+14), participants will undergo functional brain imaging sessions in the morning and evening. Between the two sessions, each participant will complete the Multidimensional Assessment of Interoceptive Awareness (MAIA-2) questionnaire and perform the Heartbeat Detection Task to evaluate interoceptive accuracy.

Study Type

Interventional

Enrollment (Estimated)

30

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 Contact

Study Contact Backup

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Person aged from 18 to 70 years
  • Only for the patients : ny patient with a diagnosis of idiopathic RLS based on medical history and the presence of the 5 RLS diagnostic criteria
  • Normal clinical examination
  • Person affiliated or benefiting from a social security scheme
  • Free, informed and written consent signed by the participant and the investigator (no later than the day of inclusion and prior to any review required by the research).

Exclusion Criteria:

  • Any significant psychiatric illness or mood disorder
  • History or presence of chronic pain other than that associated with RLS, history of epilepsy or serious head injury, history of peripheral neuropathy, diabetes
  • Clinically significant sleep apnea, narcolepsy, or any secondary causes of RLS (e.g. chronic renal failure/hemodialysis, pregnancy)
  • Other active clinically significant illness, including unstable cardiovascular, or neoplasic pathology which could interfere with the study conduct or interfere with study assessments or compromise the study participation
  • Contra-indication to MRI (pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia or refusing MRI)
  • Pregnant or breastfeeding woman
  • Persons referred to in articles L.1121-5 to L.1121-8 (persons deprived of liberty by judicial or administrative decision, minors, adults subject to a legal protection measure or unable to express their consent).

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: Other
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: healthy controls
Device: activity-rest cycle
To further investigate the mutual influence of sleep quality on RLS symptoms and mood, the activity-rest cycle will be monitored by wearable actigraph to be placed on the non-dominant wrist during a period of 13 days and 14 nights.
Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS)
To evaluate sleep quality, daytime somnolence and mood disorders (Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS)).
Device: Ecological Momentary Assessment (EMA)
4 electronic interviews administered per day during 14 days by a study-dedicated Android OS smartphone
Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
Interoceptive awareness and accuracy estimation : Adult ADHD Self-Report Scale (ASRS), Pre-Sleep Arousal Scale (PSAS), Arousal Predisposition Scale (APS) et Multidimensional Assessment of Interoceptive Awareness version 2 (MAIA-2)
Device: MRI
Morning and evening functional brain imaging
Experimental: Restless Legs Syndrome
Other: Clinical assessment
RLS history, RLS treatments, and International Restless Legs Syndrome Rating Scale (IRLSRS) will be recorded
Device: activity-rest cycle
To further investigate the mutual influence of sleep quality on RLS symptoms and mood, the activity-rest cycle will be monitored by wearable actigraph to be placed on the non-dominant wrist during a period of 13 days and 14 nights.
Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS)
To evaluate sleep quality, daytime somnolence and mood disorders (Pittsburgh Sleep Quality Index (PSQI), Insomnia Severity Index (ISI), Epworth Sleepiness Scale (ESS) and Hospital Anxiety and Depression Scale (HADS)).
Device: Ecological Momentary Assessment (EMA)
4 electronic interviews administered per day during 14 days by a study-dedicated Android OS smartphone
Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
Interoceptive awareness and accuracy estimation : Adult ADHD Self-Report Scale (ASRS), Pre-Sleep Arousal Scale (PSAS), Arousal Predisposition Scale (APS) et Multidimensional Assessment of Interoceptive Awareness version 2 (MAIA-2)
Device: MRI
Morning and evening functional brain imaging

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional Connectivity (FC) of the anterior and posterior insular cortex (IC) measured at rest.
Time Frame: 14 days after baseline (Day 0)

The investigators hypothesize that this connectivity will differ between patients and control subjects.

This outcome will be assessed through the temporal fluctuation of the BOLD signal measured during the MRI examination conducted in the morning and again in the evening.
14 days after baseline (Day 0)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlations will be explored between the scores obtained by patients and those of the healthy volunteer group on the various self-assessment scales.
Time Frame: 14 days after baseline (Day 0)

Score comparisons on these same scales will also be conducted between the patient group and the healthy volunteer group. The scores analyzed will be those obtained on the following scales:

  • International Restless Legs Syndrome Rating Scale (IRLSRS) (to assess the severity of RLS),
  • Insomnia Severity Index (ISI),
  • Adult ADHD Self-Report Scale (ASRS) (to screen for symptoms of ADHD),
  • Hospital Anxiety and Depression Scale (HADS) (to assess levels of depression and anxiety),
  • Multidimensional Assessment of Interoceptive Awareness Version 2 (MAIA-2) (to evaluate interoceptive awareness),
  • Pre-Sleep Arousal Scale (PSAS) and Arousal Predisposition Scale (APS) (to measure levels of hypervigilance),
  • Epworth Sleepiness Scale (ESS) (to assess hypersomnolence).
14 days after baseline (Day 0)
Correlations will be explored between the severity score of the RLS and sleep parameters
Time Frame: 14 days after baseline (Day 0)
assessed by actigraphy (specific measures including: Total Sleep Duration [minutes], Sleep Efficiency [%], Wake After Sleep Onset [minutes], and Sleep Onset Latency [minutes]) as well as scores from Ecological Momentary Assessment smartphone questionnaires.
14 days after baseline (Day 0)
Correlations will be explored between altered functional connectivity of the patients' insular cortex
Time Frame: 14 days after baseline (Day 0)

(measured by statistical synchrony or temporal correlation of BOLD [Blood Oxygen Level Dependent] signals across different brain regions) and sleep parameters assessed by actigraphy (specific measures including Total Sleep Duration [minutes], Sleep Efficiency [%], Wake After Sleep Onset [minutes], and Sleep Onset Latency [minutes]) as well as scores from Ecological Momentary Assessment smartphone questionnaires.

Comparisons will also be made with results obtained from the healthy volunteer group.
14 days after baseline (Day 0)

Collaborators and Investigators

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

Sponsor

University Hospital, Bordeaux

Collaborators

Restless Legs Syndrome Foundation

Investigators

  • Study Chair: Gwénaëlle CATHELINE, PhD, Université de Bordeaux - INCIA
  • Principal Investigator: Imad Marc Antoine GHORAYEB, MD, PhD, University Hospital, Bordeaux

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)

September 16, 2025

Primary Completion (Estimated)

October 1, 2026

Study Completion (Estimated)

October 1, 2026

Study Registration Dates

First Submitted

May 13, 2025

First Submitted That Met QC Criteria

May 23, 2025

First Posted (Actual)

June 3, 2025

Study Record Updates

Last Update Posted (Estimated)

September 17, 2025

Last Update Submitted That Met QC Criteria

September 16, 2025

Last Verified

September 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2024/68

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

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.

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