Restless Legs SyndromeIntoRLSNCT07001891
Functional Connectivity of the Interoceptive Network in RLS
A study testing Clinical assessment, auto-questionnaires (PSQI, ISI, ESS and HADS) and Ecological Momentary Assessment (EMA) in people with Restless Legs Syndrome, run by University Hospital, Bordeaux at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Restless Legs Syndrome
- What is being tested?
- Clinical assessment, auto-questionnaires (PSQI, ISI, ESS and HADS) and Ecological Momentary Assessment (EMA)
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 16 Sep 2025to Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Imad Marc Antoine GHORAYEB, MD, PhD contact
Fatima-Zahra MAKHOUKHI contact
France1 site, 1 recruiting
- Recruiting
CHU de Bordeaux - Neurophysiologie Clinique de l'Enfant et de l'Adulte
Bordeaux
Imad Marc-Antoine GHORAYEB, MD, PhD, (0)5.56.79.55.13 ext. +33, marc-antoine.ghorayeb@chu-bordeaux.fr
Fatima-Zahra MAKHOUKHI, fatima-zahra-makhoukhi@chu-bordeaux.fr
About this study
Official title: 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.
Read the 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.
- Conditions
- Restless Legs Syndrome
- Being tested
- Clinical assessment, auto-questionnaires (PSQI, ISI, ESS and HADS), Ecological Momentary Assessment (EMA), activity-rest cycle, auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
- Keywords
- Restless Legs Syndrome, Interoception, Insular Cortex, Functional Connectivity
- Medical subject headings
- Restless Legs Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Clinical assessmentOther
RLS history, RLS treatments, and International Restless Legs Syndrome Rating Scale (IRLSRS) will be recorded
auto-questionnaires (PSQI, ISI, ESS and HADS)Behavioural
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)).
Ecological Momentary Assessment (EMA)Device
4 electronic interviews administered per day during 14 days by a study-dedicated Android OS smartphone
activity-rest cycleDevice
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.
auto-questionnaires (ASRS, PSAS, APS, MAIA-2)Behavioural
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)
MRIDevice
Morning and evening functional brain imaging
| Study group | Role | What they receive |
|---|---|---|
| Restless Legs Syndrome | Experimental | Not described Receives: Other: Clinical assessment; Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS); Device: Ecological Momentary Assessment (EMA); Device: activity-rest cycle; Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2); Device: MRI |
| healthy controls | Active comparator | Not described Receives: Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS); Device: Ecological Momentary Assessment (EMA); Device: activity-rest cycle; Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2); Device: MRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional Connectivity (FC) of the anterior and posterior insular cortex (IC) measured at rest.
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.
Measured: 14 days after baseline (Day 0)
Secondary outcomes (3)
Correlations will be explored between the scores obtained by patients and those of the healthy volunteer group on the various self-assessment scales.
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).
Measured: 14 days after baseline (Day 0)
Correlations will be explored between the severity score of the RLS 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.
Measured: 14 days after baseline (Day 0)
Correlations will be explored between altered functional connectivity of the patients' insular cortex
(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.
Measured: 14 days after baseline (Day 0)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jun 2025
- Study start16 Sep 2025
- Primary completionDec 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bordeaux
- Sponsor type
- University, hospital or other
- Collaborators
- Restless Legs Syndrome Foundation
- Responsible party
- Sponsor
- Investigators
- Imad Marc Antoine GHORAYEB, MD, PhD, Principal investigator, University Hospital, BordeauxGwénaëlle CATHELINE, PhD, Study chair, Université de Bordeaux - INCIA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07001891
- Sponsor's protocol ID
- CHUBX 2024/68
- Other IDs
- 2024-A02497-40
- Acronym
- IntoRLS
- Status last verified
- Sep 2026
- First submitted
- 13 May 2025
- Last updated
- 25 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Connectivity of the Interoceptive Network in Restless Legs Syndrome (RLS) : an Anatomical-clinical Prospective Study Based on Daily-life Assessment
- ClinicalTrials.gov ID
- NCT07001891
- Acronym / sponsor ID
- IntoRLS / CHUBX 2024/68
- Conditions
- Restless Legs Syndrome
- Keywords
- Restless Legs Syndrome, Interoception, Insular Cortex, Functional Connectivity
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- University Hospital, BordeauxUniversity, hospital or other
- Collaborators
- Restless Legs Syndrome Foundation
- Study start
- 16 Sep 2025 (actual)
- Primary completion
- Dec 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 3 Jun 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Restless Legs Syndrome | Experimental | Other: Clinical assessment, Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS), Device: Ecological Momentary Assessment (EMA), Device: activity-rest cycle, Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2), Device: MRI |
| healthy controls | Active comparator | Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS), Device: Ecological Momentary Assessment (EMA), Device: activity-rest cycle, Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2), Device: MRI |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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).
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Clinical assessmentRLS history, RLS treatments, and International Restless Legs Syndrome Rating Scale (IRLSRS) will be recorded | Other | Restless Legs Syndrome |
| 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)). | Behavioural | Restless Legs Syndrome, healthy controls |
| Ecological Momentary Assessment (EMA)4 electronic interviews administered per day during 14 days by a study-dedicated Android OS smartphone | Device | Restless Legs Syndrome, healthy controls |
| activity-rest cycleTo 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. | Device | Restless Legs Syndrome, healthy controls |
| 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) | Behavioural | Restless Legs Syndrome, healthy controls |
| MRIMorning and evening functional brain imaging | Device | Restless Legs Syndrome, healthy controls |
Primary outcome
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.
3 secondary outcomes
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)
Correlations will be explored between the severity score of the RLS and sleep parameters
Time frame: 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)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Sep 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Imad Marc Antoine GHORAYEB, MD, PhD contact
Fatima-Zahra MAKHOUKHI contact
Imad Marc Antoine GHORAYEB, MD, PhD principal investigator
University Hospital, Bordeaux
Gwénaëlle CATHELINE, PhD study chair
Université de Bordeaux - INCIA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Clinical assessment, auto-questionnaires (PSQI, ISI, ESS and HADS) and Ecological Momentary Assessment (EMA) in people with Restless Legs Syndrome, run by University Hospital, Bordeaux at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Imad Marc Antoine GHORAYEB, MD, PhD ((0)5.56.79.55.13 ext. +33, marc-antoine.ghorayeb@chu-bordeaux.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Functional Connectivity (FC) of the anterior and posterior insular cortex (IC) measured at rest. (time frame: 14 days after baseline (Day 0)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026.