Efficacy of Fluoxetine Against Seizure-induced Central Apneas

NCT02569970 | Completed Phase 3 DMC

• 1 other identifier: 2009-562
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

Sudden unexpected death in epilepsy (SUDEP) is a tragic outcome of seizure disorders that primarily affect young adults suffering from refractory epilepsy. In this population, SUDEP incidence is estimated at 0.5%. While the mechanisms of SUDEP are not completely understood, it appears that the majority of such death occurs in the immediate aftermath of a general tonic-clonic seizure. There is currently no validated preventive treatment for SUDEP. Some evidence suggest that modulation of the serotoninergic tone, and more specifically selective serotonin recapture inhibitor (SSRI) such as fluoxetine, might prevent SUDEP. Indeed, fluoxetine prevents seizure-induced lethal central apneas in DBA/2 and DBA/1 mice, one of the few animal models of SUDEP. Furthermore, serotoninergic bulbar nuclei are known to play a major role in the control of breathing, especially during sleep and in response to repeated hypoxia. In patients with epilepsy undergoing in-hospital video-EEG monitoring, about one third of seizures are associated with decrease in SpO2 \<90%, an abnormality suspected to represent a risk factor of SUDEP. In a retrospective uncontrolled study, patients treated with SSRIs displayed less frequent ictal/post-ictal hypoxemia than patients not taking SSRIs. The investigators project aimed at testing whether fluoxetine can reduce the risk of ictal/post-ictal hypoxemia by performing a double-blind, randomized, placebo-controlled trial in patients undergoing video-EEG monitoring as part of the pre-surgical evaluation of their focal drug-resistant epilepsy.

Conditions

Epilepsy; Ictal/Post-ictal Hypoxemia

Keywords

Epilepsy; SUDEP; fluoxetine; placebo; SpO2

Outcome Measures

Primary Outcomes (1)

• Ictal/post-ictal hypoxemia

  Percentage of patients with at least one seizure associated with ictal/post-ictal SpO2 \<90% in the group treated with fluoxetine compared to that receiving placebo.

  Duration of video-EEG following 4 weeks of fluoxetine treatment

Secondary Outcomes (6)

• Change in mood score with BDI-II score

  After four weeks of treatment as compared to baseline

• Change in mood score with NDDIE score

  After four weeks of treatment as compared to baseline

• Change in seizure frequency

  After four weeks of treatment as compared to baseline

• Change in sleep disorders score with SASDQ score

  After four weeks of treatment as compared to baseline

• Change in sleep disorders score with EPWORTH score

  After four weeks of treatment as compared to baseline

Study Arms (2)

FLUOXETINE

ACTIVE COMPARATOR

4 weeks of treatment before video-EEG monitoring

Drug: fluoxetine 20 mg

PLACEBO

PLACEBO COMPARATOR

1 month of treatment before EEG video.

Drug: placebo 20 mg

Interventions

fluoxetine 20 mg DRUG

Fluoxetine 20 mg per day during 4 weeks prior to video-EEG, then continued during video-EEG. At the end of video-EEG, and according to patient's decision, treatment was either progressively withdrawn (1 week at 10 mg per day and then 1 week at 5 mg per day), or replaced by fluoxetine 20 mg open-label.

FLUOXETINE

placebo 20 mg DRUG

Placebo 20 mg per day during 4 weeks prior to video-EEG, then continued during video-EEG. At the end of video-EEG, and according to patient's decision, treatment was either progressively withdrawn (1 week at 10 mg per day and then 1 week at 5 mg per day), or replaced by fluoxetine 20 mg open-label.

PLACEBO

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient suffering from drug-resistant focal epilepsy
• Age ≥ 18 years
• Patient for whom a video-EEG monitoring of their seizures was scheduled as part of a pre-surgical assessment
• For women of childbearing age, a method of contraception considered effective by the investigator
• Patient who have given their written informed consent
• Patient accepting an interview with a psychologist and to be refered to a psychiatrist in the event that mood disorders were detected on mood scores and considered severe by the investigator and / or psychologist, leading to require psychiatric care or immediate antidepressant treatment
• Patient with a social security number

You may not qualify if:

• Age \< 18 years
• Patient under legal protection
• Pregnant or breastfeeding women
• Hypersensitivity to fluoxetine or its excipients
• History of other serious side effects related to an earlier prescription of fluoxetine;
• Current suicidal ideation or history of suicide attempt
• Manic episode
• Disruption of liver enzymes considered material by the investigator using the following criteria:
• transaminases (ALT and AST)\> 2N alkaline phosphatase (ALP)\> 2N gamma glutamyl transpeptidase (GGT)\> 5N (performed as part of routine monitoring of epileptic patients on antiepileptic treatment. Patients often exhibit changed deemed clinically insignificant due to the enzyme-inducing effect of these drugs)
• Renal failure with creatinine clearance \<30 ml / min
• Acute heart disease
• Antidepressant treatment
• Other prohibited treatment (see detailed list in protocol).

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (1)

Service de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique

Lyon, France

Location

MeSH Terms

Conditions

Epilepsy; Sudden Unexpected Death in Epilepsy

Interventions

Fluoxetine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Death, Sudden; Death; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals

Study Officials

• Philippe RYVLIN, Professor

  Hospices Civils de Lyon

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2015
• First Posted: October 7, 2015
• Study Start: November 1, 2010
• Primary Completion: December 1, 2010
• Study Completion: January 1, 2015
• Last Updated: October 5, 2016

Record last verified: 2016-10

Locations

FR (1)