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Efficacy of Fluoxetine Against Seizure-induced Central Apneas (FLUOXETINE)

Primary Purpose

Epilepsy, Ictal/Post-ictal Hypoxemia

Status

Completed

Phase

Phase 3

Locations

France

Study Type

Interventional

Intervention

fluoxetine 20 mg

placebo 20 mg

About this trial

This is an interventional treatment trial for Epilepsy focused on measuring Epilepsy, SUDEP, fluoxetine, placebo, SpO2

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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

Exclusion Criteria:

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).

Sites / Locations

Service de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

FLUOXETINE

PLACEBO

Arm Description

4 weeks of treatment before video-EEG monitoring

1 month of treatment before EEG video.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in mood score with BDI-II score

Changes in score of BDI-II after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Change in mood score with NDDIE score

Changes in score of NDDIE after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Change in seizure frequency

Changes in seizure frequency after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Change in sleep disorders score with SASDQ score

Changes in score of SASDQ after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Change in sleep disorders score with EPWORTH score

Changes in score of EPWORTH after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Change in score of quality of life

Change in score of QOLIE-89 after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Full Information

NCT ID

NCT02569970

First Posted

September 24, 2015

Last Updated

October 4, 2016

Sponsor

Hospices Civils de Lyon

1. Study Identification

Unique Protocol Identification Number

NCT02569970

Brief Title

Efficacy of Fluoxetine Against Seizure-induced Central Apneas

Acronym

FLUOXETINE

Official Title

Efficacy of Fluoxetine Against Seizure-induced Central Apneas : a Randomized Placebo-controled Double-blind Trial.

Study Type

Interventional

2. Study Status

Record Verification Date

October 2016

Overall Recruitment Status

Completed

Study Start Date

November 2010 (undefined)

Primary Completion Date

December 2010 (Actual)

Study Completion Date

January 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Hospices Civils de Lyon

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Epilepsy, Ictal/Post-ictal Hypoxemia

Keywords

Epilepsy, SUDEP, fluoxetine, placebo, SpO2

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

70 (Actual)

8. Arms, Groups, and Interventions

Arm Title

FLUOXETINE

Arm Type

Active Comparator

Arm Description

4 weeks of treatment before video-EEG monitoring

Arm Title

PLACEBO

Arm Type

Placebo Comparator

Arm Description

1 month of treatment before EEG video.

Intervention Type

Drug

Intervention Name(s)

fluoxetine 20 mg

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

placebo 20 mg

Intervention Description

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.

Primary Outcome Measure Information:

Title

Ictal/post-ictal hypoxemia

Description

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.

Time Frame

Duration of video-EEG following 4 weeks of fluoxetine treatment

Secondary Outcome Measure Information:

Title

Change in mood score with BDI-II score

Description

Changes in score of BDI-II after four weeks of treatment as compared to baseline in the group treated with fluoxetine compared to that receiving placebo

Time Frame