Brief Summary

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.

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

participants targeted

Target at P25-P50 for not_applicable

Timeline

8mo left

Started Nov 2024

Typical duration for not_applicable

Geographic Reach

1 country

1 active site

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

2.2 years study duration

Study Progress69%

Nov 2024Jan 2027

First Submitted

Initial submission to the registry

August 1, 2024

Completed

8 days until next milestone

First Posted

Study publicly available on registry

August 9, 2024

Completed

3 months until next milestone

Study Start

First participant enrolled

November 4, 2024

Completed

2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 4, 2027

Expected

Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 4, 2027

Last Updated

March 27, 2026

Status Verified

March 1, 2026

Enrollment Period

2.2 years

First QC Date

August 1, 2024

Last Update Submit

March 24, 2026

Conditions

Epilepsy

Keywords

EpilepsySUDEPGTCSDrug-resistantArousalHypercanic challenge

Outcome Measures

Primary Outcomes (1)

End tidal CO2 (PETCO2) value at arousal in patients with epilepsy and in healthly subjects
PETCO2 corresponds to the value taken at the end of a breath of the partial pressure of CO2. Two hypercapnic challenges will be performed the same night. The first will start once unequivocal N3 stage of NREM will be observed, as determined online by polysomnography data. After the termination of the first test, the patient/subject will go back to sleep and a second procedure will be performed once she/he will reach N3 stage of NREM again. Data from the two procedures will be averaged for each subject.
the night of hospitalization

Secondary Outcomes (8)

Value of the HCVR slope during sleep in patients with epilepsy and in healthy subjects
one night of hospitalization
Value of the awake HCVR slope in patients with epilepsy and in healthly subjects
will be measured during hypercapnic challenges on awakening on the first day of hospitalization.
Value of the ventilatory recruitment threshold (VRT) in patients with epilepsy and in healthly subjects
will be measured during hypercapnic challenges on awakening on the first day of hospitalization.
Number of focal to bilateral tonic-clonic seizures during the 3 months preceding the polysomnography in patients with epilepsy
Will be collected during the first day of hospitalization
Central apnea index and Obstructive Apnea Hypopnea Index
one night of hospitalization
+3 more secondary outcomes

Study Arms (2)

Patients with drug-resistant focal epilepsy

OTHER

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

Procedure: Video-EEG monitoringProcedure: Respiratory monitoring and polysomnographyProcedure: 1 Hypercapnic challenge while participant is awakeProcedure: 2 Hypercapnic challenges while participant is sleepingProcedure: Auditory stimulusOther: Questionnaires

Healthy subjects

OTHER

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