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Caracterization of the Combined Alterations in Respiration and AROUSal in Patients with Drug-resistant EpiLepsy (CARROUSEL)

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Civil Hospices of Lyon

Status

Enrolling

Conditions

Epilepsy

Treatments

Procedure: 2 Hypercapnic challenges while participant is sleeping
Procedure: Video-EEG monitoring
Procedure: 1 Hypercapnic challenge while participant is awake
Other: Questionnaires
Procedure: Respiratory monitoring and polysomnography
Procedure: Auditory stimulus

Study type

Interventional

Funder types

Other

Identifiers

NCT06545214
69HCL23_1350

Details and patient eligibility

About

30% of patients with epilepsy suffer from drug-resistant seizures and are at risk of epilepsy-related complications, from cognitive dysfunctions to premature mortality. Both seizures and their complications are modulated by patients' vigilance states, with a tight and bi-directional interplay between sleep and epilepsy. Several epilepsy complications are associated with sleep, such as sleep-disordered breathing or Sudden and Unexpected Death in Epilepsy (SUDEP). SUDEP is a non-traumatic death, unrelated to a documented status epilepticus, which accounts for up 50% of premature deaths in epilepsy, with a cumulative risk of ≈ 10% at 40 years in patients with childhood-onset epilepsy. SUDEP typically occurs during sleep, after a nocturnal seizure, and primarily results from a postictal central respiratory dysfunction in patients with generalized convulsive seizure (GCS), suggesting that interaction between respiratory dysfunction and sleep state may play a role in its pathophysiology.

Most of patients with drug-resistant seizures demonstrate transient peri-ictal apnea and hypoxemia, especially in the aftermath of a GCS. Experimental and clinical data suggest that most SUDEP primarily result from a fatal seizure-related respiratory arrest. In patients whose SUDEP had occurred during long-term video-EEG monitoring, we observed fatal postictal central apnea after a nocturnal GCS in all SUDEP. Accordingly, it is currently hypothesized that in a subgroup of patients, repetition of seizures may contribute to chronic alteration of respiratory regulation which may increase the risk of fatal postictal central respiratory arrest. Finally, post-mortem data in SUDEP patients showed alteration of neuronal populations involved in respiratory control in the medulla.

The complex network that regulates arousal and sleep and the respiratory network are strongly interconnected. Impairment of the interaction between central respiratory control and arousal systems has been reported in several clinical situations, including sleep apnea syndrome, sudden infant death syndrome or Prader-Willi Syndrome. In epilepsy, preclinical data in rodents indirectly support a role for 5HT in the impairment of the interactions between the arousal and respiratory systems in the cascade of events leading to SUDEP. However, no direct evidence is available, and the link between alterations of the brainstem networks involved in arousal regulation and respiratory dysfunction has not been characterized in patients with epilepsy yet.

Enrollment

60 estimated patients

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Patients :

  1. Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study

  2. Aged 18 to 55 years old

  3. Diagnosis of focal epilepsy

  4. Epilepsy is refractory to treatment, as defined by the International League Against Epilepsy

  5. Patients with ≥3 focal to bilateral tonic-clonic seizure (FBTCS) during the past 18 months

  6. Patients who had undergone long-term video-EEG (VEEG) monitoring for presurgical evaluation in the past ten years within the Department of Functional Neurology and Epileptology at Hospices Civils de Lyon, ensuring access to detailed information about:

    • occurrence of transient respiratory dysfunction during the focal seizures, transient hypoxemia during strictly focal seizures being observed in 40% of patients(39) and in 87% of patients with at least one FBTCS during the VEEG monitoring(46)
    • localization of the epileptogenic zone, the risk of peri-ictal respiratory dysfunction being greater in seizures of temporal lobe origin than in extra-temporal seizures, even after FBTCS

Healthy subjects

  1. Written informed consent obtained from study subject and ability for study subject to comply with the requirements of the study
  2. Aged 18 to 55 years old

Exclusion criteria

Patients

  1. Ongoing or chronic respiratory and/or cardiac insufficiency
  2. Obstructive sleep-apnea syndrome
  3. Ongoing treatment with selective serotonin reuptake inhibitor
  4. Patient treated with vagal nerve stimulation
  5. Pregnant women or breastfeeding women, based on declarations at V0
  6. Persons receiving psychiatric care
  7. Persons deprived of their liberty by a judicial or administrative decision
  8. Adults subject to a legal protection measure (guardianship, curatorship)
  9. Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
  10. Positive urine pregnancy test at V1, if applicable

Healthy subjects

  1. History of epilepsy
  2. Ongoing or chronic respiratory and/or cardiac insufficiency
  3. Obstructive sleep-apnea syndrome
  4. Pregnant women, women in labor or breastfeeding women, based on declarations at V0
  5. Persons receiving psychiatric care
  6. Persons deprived of their liberty by a judicial or administrative decision
  7. Adults subject to a legal protection measure (guardianship, curatorship)
  8. Persons not affiliated to a social security scheme or beneficiaries of a similar scheme
  9. Positive urine pregnancy test at V1, if applicable

Trial design

Primary purpose

Basic Science

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

60 participants in 2 patient groups

Patients with drug-resistant focal epilepsy
Other group
Description:
Patients with \>3 focal to bilateral tonic-clonic seizure per year and who had undergone long-term video-EEG (VEEG) monitoring for presurgical evaluation. After a prospective baseline, which will allow to ensure prospective seizure count for patients with epilepsy, all participants will undergo a 24-hours hospitalization. The following procedures will be carried out as part of the research: * Video-EEG recordings * Respiratory monitoring * Full-night polysomnography * 1 Hypercapnic challenge while participant is awake * 2 Hypercapnic challenges while participant is sleeping * Auditory stimulus All the medical devices used in this study are already in routine use at Hospices Civils de Lyon
Treatment:
Procedure: Auditory stimulus
Other: Questionnaires
Procedure: Respiratory monitoring and polysomnography
Procedure: 1 Hypercapnic challenge while participant is awake
Procedure: Video-EEG monitoring
Procedure: 2 Hypercapnic challenges while participant is sleeping
Healthy subjects
Other group
Description:
Selection of healthy subjects will be performed to ensure age-matching. After a prospective baseline, which will allow to ensure prospective seizure count for patients with epilepsy, all participants will undergo a 24-hours hospitalization. The following procedures will be carried out as part of the research: * Video-EEG recordings * Respiratory monitoring * Full-night polysomnography * 1 Hypercapnic challenge while participant is awake * 2 Hypercapnic challenges while participant is sleeping * Auditory stimulus All the medical devices used in this study are already in routine use at Hospices Civils de Lyon
Treatment:
Procedure: Auditory stimulus
Other: Questionnaires
Procedure: Respiratory monitoring and polysomnography
Procedure: 1 Hypercapnic challenge while participant is awake
Procedure: Video-EEG monitoring
Procedure: 2 Hypercapnic challenges while participant is sleeping

Trial contacts and locations

1

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Central trial contact

Sylvain Pr Rheims; Mathilde LECLERCQ

Data sourced from clinicaltrials.gov

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