Serotoninergic Pathways in Sudden and Unexpted Death in Epilepsy (SUDEP)

Terminated

• Conditions: Sudden Unexpected Death in Epilepsy (SUDEP)
• Interventions: Other: Brain samples; Other: Skin samples

• Registration Number: NCT02788318
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

The mortality rate is increased in patients with epilepsy, and especially among patients with drug-resistant epilepsy. This increased mortality is mainly related to the risk of SUDEP whose incidence is between 3.5 and 9 per 1,000 for patients with drug-resistant epilepsy. The term SUDEP refers to a sudden death occurring in a patient with epilepsy in whom anamnestic and post-mortem evidence does not identify a particular cause. Experimental and clinical data strongly suggest that most of SUDEP result from a postictal respiratory dysfunction progressing to terminal apnea. Due to the major role of serotonin in regulating breathing rhythms and data in animal models of epilepsy, it is envisaged that an alteration of serotonergic systems of the brainstem and limbic regions may play a central role in the occurrence of SUDEP. The objective of this work is to look for abnormalities of the serotonergic transmission within regulatory regions of respiratory and autonomic functions in brain samples prospectively collected in patients died from SUDEP.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2014-01
• Study First Submitted: 2016-05-27
• Study First Submitted QC: 2016-05-27
• Study First Posted: 2016-06-02
• Primary Completion: 2019-01
• Study Completion: 2019-01
• Status Verified: 2019-04
• Last Update Submitted: 2019-04-01
• Last Update Posted: 2019-04-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

Inclusion Criteria

• Age >18 years
• Postmortem time before autopsy <30 hours

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Exclusion Criteria

• Age <18 years
• postmortem time before autopsy > 30 hours
• Any subject whose brain would be of forensic interest
• Any patient who expressed an opposition to organ donation.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control 2	Brain samples	Subjects without known pathological history, remained victims of unexplained sudden unexpected death (SUDEP) after all investigations and for which a heart rhythm disorder is suspected in first intention. Brain samples and skin samples are collected.
diagnostic of SUDEP	Brain samples	patient with epilepsy in whom anamnestic and post-mortem evidence does not identify a particular cause (diagnosis of SUDEP). Brain samples and skin samples are collected.
Control 2	Skin samples	Subjects without known pathological history, remained victims of unexplained sudden unexpected death (SUDEP) after all investigations and for which a heart rhythm disorder is suspected in first intention. Brain samples and skin samples are collected.
diagnostic of SUDEP	Skin samples	patient with epilepsy in whom anamnestic and post-mortem evidence does not identify a particular cause (diagnosis of SUDEP). Brain samples and skin samples are collected.
Control 1	Brain samples	Subjects with a known epilepsy, whose death is linked to a specific cause. Brain samples and skin samples are collected.
Control 1	Skin samples	Subjects with a known epilepsy, whose death is linked to a specific cause. Brain samples and skin samples are collected.

Primary Outcome Measures

Name	Time	Method
Density of Medullary 5-HT Neurons	between 1 to 30 hours following death	5-HT1A receptor binding density in within the medulla

Secondary Outcome Measures

Name	Time	Method
Other markers of 5HT within the medulla	between 1 to 30 hours following death	Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2)
Serotoninergic pathway in the pons, the hippocampus and the insula	between 1 to 30 hours following death	5-HT1A receptor binding density, Expression of 5HT-1A and 5HT-2 receptors, expression of 5HT transporter, Tryptophan Hydroxylase 2 (TPH2)
Catecholaminergic pathway	between 1 to 30 hours following death	Number of neurons expressing the tyrosine hydroxylase, expression of alpha and beta adrenergic receptors, expression of dopamine-bêta-hydroxylase

Trial Locations

Locations (1)

Hospices Civils de Lyon - Institut Médico-Légal; 🇫🇷 Lyon, France