EpilepsyPhase 3FLUOXETINENCT02569970
Efficacy of Fluoxetine Against Seizure-induced Central Apneas
A Phase 3 study testing fluoxetine 20 mg in people with Epilepsy and Ictal/Post-ictal Hypoxemia, run by Hospices Civils de Lyon at 1 site in France.
Trial 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%. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Epilepsy, Ictal/Post-ictal Hypoxemia
- What is being tested?
- fluoxetine 20 mg
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 70 participants
- Where
- 1 siteFrance
- Study dates
- Nov 2010to Jan 2015
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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).
Trial locations and contacts
1 site in 1 country.
France1 site
Service de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique
Lyon
About this study
Official title: Efficacy of Fluoxetine Against Seizure-induced Central Apneas : a Randomized Placebo-controled Double-blind Trial.
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.
Read more
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
- Being tested
- fluoxetine 20 mg, placebo 20 mg
- Keywords
- Epilepsy, SUDEP, fluoxetine, placebo, SpO2
- Medical subject headings
- Epilepsy, Sudden Unexpected Death in Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fluoxetine 20 mgDrug
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 mgDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| FLUOXETINE | Active comparator | 4 weeks of treatment before video-EEG monitoring Receives: Drug: fluoxetine 20 mg |
| PLACEBO | Placebo comparator | 1 month of treatment before EEG video. Receives: Drug: placebo 20 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Duration of video-EEG following 4 weeks of fluoxetine treatment
Secondary outcomes (6)
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
Measured: After four weeks of treatment as compared to baseline
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
Measured: After four weeks of treatment as compared to baseline
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
Measured: After four weeks of treatment as compared to baseline
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
Measured: After four weeks of treatment as compared to baseline
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
Measured: After four weeks of treatment as compared to baseline
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
Measured: After four weeks of treatment as compared to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2015 (estimated)
- Study startNov 2010
- Primary completionDec 2010
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Philippe RYVLIN, Professor, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02569970
- Sponsor's protocol ID
- 2009-562
- Acronym
- FLUOXETINE
- Status last verified
- Oct 2016
- First submitted
- 24 Sep 2015
- Last updated
- 5 Oct 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Fluoxetine Against Seizure-induced Central Apneas : a Randomized Placebo-controled Double-blind Trial.
- ClinicalTrials.gov ID
- NCT02569970
- Acronym / sponsor ID
- FLUOXETINE / 2009-562
- Conditions
- Epilepsy, Ictal/Post-ictal Hypoxemia
- Keywords
- Epilepsy, SUDEP, fluoxetine, placebo, SpO2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- Nov 2010
- Primary completion
- Dec 2010 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 7 Oct 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FLUOXETINE | Active comparator | Drug: fluoxetine 20 mg4 weeks of treatment before video-EEG monitoring |
| PLACEBO | Placebo comparator | Drug: placebo 20 mg1 month of treatment before EEG video. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (13 listed)
- Age < 18 years
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| fluoxetine 20 mgFluoxetine 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. | Drug | FLUOXETINE |
| placebo 20 mgPlacebo 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. | Drug | PLACEBO |
Primary outcome
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.
6 secondary outcomes
Change in mood score with BDI-II score
Time frame: After four weeks of treatment as compared to baseline
Change in mood score with NDDIE score
Time frame: After four weeks of treatment as compared to baseline
Change in seizure frequency
Time frame: After four weeks of treatment as compared to baseline
Change in sleep disorders score with SASDQ score
Time frame: After four weeks of treatment as compared to baseline
Change in sleep disorders score with EPWORTH score
Time frame: After four weeks of treatment as compared to baseline
Change in score of quality of life
Time frame: After four weeks of treatment as compared to baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Philippe RYVLIN, Professor study director
Hospices Civils de Lyon
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing fluoxetine 20 mg in people with Epilepsy and Ictal/Post-ictal Hypoxemia, run by Hospices Civils de Lyon at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ictal/post-ictal hypoxemia (time frame: Duration of video-EEG following 4 weeks of fluoxetine treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2016.