Caracterization of the Combined Alterations in Respiration and aROUSal in Patients With Drug-resistant EpiLepsy

NCT ID: NCT06545214

Last Updated: 2026-01-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-11-04

Study Completion Date

2027-01-04

Brief Summary

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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.

Detailed Description

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Conditions

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Epilepsy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Monocentric prospective non-randomized study comparing the arousal and respiratory responses to hypercapnia in adult patients with drug-resistant epilepsy and in healthy subjects
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Patients with drug-resistant focal epilepsy

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

Group Type OTHER

Video-EEG monitoring

Intervention Type PROCEDURE

Video-EEG monitoring

Respiratory monitoring and polysomnography

Intervention Type PROCEDURE

heart rate, pulse oximetry (oxygen levels in the blood), nasal airflow, respiratory effort (thoracic and abdominal) and capnography (carbon dioxide (CO2) levels in exhaled air)

1 Hypercapnic challenge while participant is awake

Intervention Type PROCEDURE

The healthy patient/subject breathes through the mouth, using a mouthpiece and a nose clip, through a device fitted with a hermetically sealed bag that measures the various parameters of his/her breathing. At the start of the test, the healthy patient/subject breathes ambient air and his or her breathing is measured. Then, after a few minutes, the healthy patient/subject is connected to the bag, breathing in a closed circuit. This causes a gradual increase in carbon dioxide (CO2) in the inspired air. During this time, breathing parameters will be measured and gas exchanges studied with each breath. The test is stopped when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in the event of intolerance.

2 Hypercapnic challenges while participant is sleeping

Intervention Type PROCEDURE

In the evening, as soon as the doctor detects on the EEG that the patient/subject is in deep sleep, various tests will be carried out to assess reactivity to wakefulness.

Two hypercapnic challenges will be carried out during sleep, using the same procedure as for wakefulness. The test will be stopped when the healthy patient/subject wakes up, or when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in case of intolerance.

Auditory stimulus

Intervention Type PROCEDURE

Two auditory stimulus tests will be carried out during the patient's sleep. Using headphones, the investigator will administer auditory stimuli at regular, progressively louder intervals to determine the ability of the patient/ healthy subject to awaken to an auditory stimulus.

Questionnaires

Intervention Type OTHER

Questionnaire to assess caffeine consumption habits Quality of life questionnaires QOLIE-31 Anxiety and depression questionnaires HADS

Healthy subjects

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

Group Type OTHER

Video-EEG monitoring

Intervention Type PROCEDURE

Video-EEG monitoring

Respiratory monitoring and polysomnography

Intervention Type PROCEDURE

heart rate, pulse oximetry (oxygen levels in the blood), nasal airflow, respiratory effort (thoracic and abdominal) and capnography (carbon dioxide (CO2) levels in exhaled air)

1 Hypercapnic challenge while participant is awake

Intervention Type PROCEDURE

The healthy patient/subject breathes through the mouth, using a mouthpiece and a nose clip, through a device fitted with a hermetically sealed bag that measures the various parameters of his/her breathing. At the start of the test, the healthy patient/subject breathes ambient air and his or her breathing is measured. Then, after a few minutes, the healthy patient/subject is connected to the bag, breathing in a closed circuit. This causes a gradual increase in carbon dioxide (CO2) in the inspired air. During this time, breathing parameters will be measured and gas exchanges studied with each breath. The test is stopped when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in the event of intolerance.

2 Hypercapnic challenges while participant is sleeping

Intervention Type PROCEDURE

In the evening, as soon as the doctor detects on the EEG that the patient/subject is in deep sleep, various tests will be carried out to assess reactivity to wakefulness.

Two hypercapnic challenges will be carried out during sleep, using the same procedure as for wakefulness. The test will be stopped when the healthy patient/subject wakes up, or when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in case of intolerance.

Auditory stimulus

Intervention Type PROCEDURE

Two auditory stimulus tests will be carried out during the patient's sleep. Using headphones, the investigator will administer auditory stimuli at regular, progressively louder intervals to determine the ability of the patient/ healthy subject to awaken to an auditory stimulus.

Questionnaires

Intervention Type OTHER

Questionnaire to assess caffeine consumption habits Quality of life questionnaires QOLIE-31 Anxiety and depression questionnaires HADS

Interventions

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Video-EEG monitoring

Video-EEG monitoring

Intervention Type PROCEDURE

Respiratory monitoring and polysomnography

heart rate, pulse oximetry (oxygen levels in the blood), nasal airflow, respiratory effort (thoracic and abdominal) and capnography (carbon dioxide (CO2) levels in exhaled air)

Intervention Type PROCEDURE

1 Hypercapnic challenge while participant is awake

The healthy patient/subject breathes through the mouth, using a mouthpiece and a nose clip, through a device fitted with a hermetically sealed bag that measures the various parameters of his/her breathing. At the start of the test, the healthy patient/subject breathes ambient air and his or her breathing is measured. Then, after a few minutes, the healthy patient/subject is connected to the bag, breathing in a closed circuit. This causes a gradual increase in carbon dioxide (CO2) in the inspired air. During this time, breathing parameters will be measured and gas exchanges studied with each breath. The test is stopped when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in the event of intolerance.

Intervention Type PROCEDURE

2 Hypercapnic challenges while participant is sleeping

In the evening, as soon as the doctor detects on the EEG that the patient/subject is in deep sleep, various tests will be carried out to assess reactivity to wakefulness.

Two hypercapnic challenges will be carried out during sleep, using the same procedure as for wakefulness. The test will be stopped when the healthy patient/subject wakes up, or when the end-tidal carbon dioxide pressure (PetCO2) reaches 60 mm Hg, or in case of intolerance.

Intervention Type PROCEDURE

Auditory stimulus

Two auditory stimulus tests will be carried out during the patient's sleep. Using headphones, the investigator will administer auditory stimuli at regular, progressively louder intervals to determine the ability of the patient/ healthy subject to awaken to an auditory stimulus.

Intervention Type PROCEDURE

Questionnaires

Questionnaire to assess caffeine consumption habits Quality of life questionnaires QOLIE-31 Anxiety and depression questionnaires HADS

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

55 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Hospices Civils de Lyon

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Hôpital Pierre Wertheimer

Bron, Rhone, France

Site Status RECRUITING

Countries

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France

Central Contacts

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Sylvain Pr Rheims

Role: CONTACT

0472357106 ext. +33

Mathilde LECLERCQ

Role: CONTACT

0472355838 ext. +33

Facility Contacts

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Sylvain Rheims, PR

Role: primary

0472357106 ext. +33

Other Identifiers

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69HCL23_1350

Identifier Type: -

Identifier Source: org_study_id

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