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Functional Connectivity of the Interoceptive Network in RLS (IntoRLS)

U

University Hospital of Bordeaux

Status

Not yet enrolling

Conditions

Restless Legs Syndrome

Treatments

Other: Clinical assessment
Device: MRI
Device: activity-rest cycle
Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS)
Device: Ecological Momentary Assessment (EMA)

Study type

Interventional

Funder types

Other

Identifiers

NCT07001891
CHUBX 2024/68

Details and patient eligibility

About

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.

Full 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.

Enrollment

30 estimated patients

Sex

All

Ages

18 to 70 years old

Volunteers

Accepts Healthy Volunteers

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).

Trial design

Primary purpose

Other

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

30 participants in 2 patient groups

Restless Legs Syndrome
Experimental group
Treatment:
Device: Ecological Momentary Assessment (EMA)
Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS)
Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
Device: activity-rest cycle
Device: MRI
Other: Clinical assessment
healthy controls
Active Comparator group
Treatment:
Device: Ecological Momentary Assessment (EMA)
Behavioral: auto-questionnaires (PSQI, ISI, ESS and HADS)
Behavioral: auto-questionnaires (ASRS, PSAS, APS, MAIA-2)
Device: activity-rest cycle
Device: MRI

Trial contacts and locations

1

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Central trial contact

Imad Marc Antoine GHORAYEB, MD, PhD; Fatima-Zahra MAKHOUKHI

Data sourced from clinicaltrials.gov

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