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Completed

NCT Number: NCT02569970

Efficacy of Fluoxetine Against Seizure-induced Central Apneas

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.

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Key information

Conditions

Epilepsy Brain Diseases Central Nervous System Diseases Death Death, Sudden Ictal/Post-ictal Hypoxemia Nervous System Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Sudden Unexpected Death in Epilepsy

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Service de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique

Lyon, France

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

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.

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.

Primary outcomes

  1. Ictal/post-ictal hypoxemia

    Time frame: Duration of video-EEG following 4 weeks of fluoxetine treatment

    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 outcomes

  1. Change in mood score with BDI-II score

    Time frame: After four weeks of treatment as compared to baseline

    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

  2. Change in mood score with NDDIE score

    Time frame: After four weeks of treatment as compared to baseline

    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

  3. Change in seizure frequency

    Time frame: After four weeks of treatment as compared to baseline

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

  4. Change in sleep disorders score with SASDQ score

    Time frame: After four weeks of treatment as compared to baseline

    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

  5. Change in sleep disorders score with EPWORTH score

    Time frame: After four weeks of treatment as compared to baseline

    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

  6. Change in score of quality of life

    Time frame: After four weeks of treatment as compared to baseline

    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

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

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

Acronym: FLUOXETINE

Important dates

Study start
2010
Primary completion
2010
Study completion
2015
First posted
Oct 7, 2015
Registry last updated
Oct 5, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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