Refractory EpilepsyPhase 4FENDEEPNCT05232630
Fenfluramine for the Treatment of Different Types of Developmental and Epileptic Encephalopathies: a Pilot Trial Exploring Epileptic and Non-epileptic Outcomes
A Phase 4 study testing Fenfluramine in people with Refractory Epilepsy and SYNGAP1 Encephalopathy, run by Hospital Ruber Internacional at 1 site in Spain.
Trial summary
This study is a pilot non-controlled clinical trial with adjunctive fenfluramine for the treatment of five different types of developmental and epileptic encephalopathies (DEEs) focused on epileptic and "non-epileptic outcomes": SYNGAP1 and STXBP1 encephalopathies, inv-dup(15) encephalopathy, multifocal or bilateral… Read more about this study
- Who is it for?
- Ages 2 to 35 years
- Conditions the study is for
- Refractory Epilepsy, SYNGAP1 Encephalopathy, STXBP1 Encephalopathy With Epilepsy
- What is being tested?
- Fenfluramine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteSpain
- Study dates
- 20 Oct 2022to 31 Dec 2024
- Phase
- Phase 4
- 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 2 to 35 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
None listed.
Who cannot join
- Subjects who meet any of the following exclusion criteria will not be enrolled into the study:
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
- Subject has only non-motor seizures (such as absences), for group 1.
- Subject has pulmonary arterial hypertension.
- Subject has current or past history of cardiovascular or cerebrovascular disease.
- Subject has current or recent history of Anorexia Nervosa, bulimia, or depression within the prior year that required medical treatment or psychological treatment for a duration greater than 1 month.
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- Subject has a current or past history of glaucoma.
- Subject has moderate or severe renal or hepatic impairment.
- Subject is receiving concomitant therapy with any of the following: centrally-acting anorectic agents; monoamine-oxidase inhibitors; any centrally-acting compound with clinically appreciable amount of serotonin agonist or antagonist properties, including serotonin reuptake inhibition; other centrally-acting noradrenergic agonists.
- Subject is currently receiving an investigational product.
- Subject has participated in another clinical trial within the past 30 days (calculated from that study's last scheduled visit).
- Subject is at imminent risk of self-harm or harm to others.
- Subject is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures, and study restrictions.
- Subject is institutionalized in a general nursing home (i.e., in a facility that does not provide skilled epilepsy care).
- Subject does not have a reliable caregiver who can provide seizure diary information throughout the study.
- Subject has a severe clinically significant condition.
Trial locations and contacts
1 site in 1 country.
About this study
This study is a pilot non-controlled clinical trial with adjunctive fenfluramine for the treatment of five different types of developmental and epileptic encephalopathies (DEEs) focused on epileptic and "non-epileptic outcomes": SYNGAP1 and STXBP1 encephalopathies, inv-dup(15) encephalopathy, multifocal or bilateral malformations of cortical development, and continuous spikes and waves during sleep. The main goal is to assess changes in seizure frequency comparing before and after treatment with fenfluramine in five specific types of developmental and epileptic encephalopathies (DEEs). Secondary objectives of this study are the analysis of changes in seizure intensity and duration, and "non-epileptic outcomes" such as variations in cognitive activity, level of alertness, impulsivity/self-control, gait stability and other alterations that might be detected during the interview and physical examination.
- Conditions
- Refractory Epilepsy, SYNGAP1 Encephalopathy, STXBP1 Encephalopathy With Epilepsy, Inv Dup(15) Encephalopathy, Multifocal or Bilateral Malformations of Cortical Development, Continuous Spike and Waves During Slow Sleep
- Being tested
- Fenfluramine
- Keywords
- refractory epilepsy, SYNGAP1, STXBP1, Inv Dup(15), developmental and epileptic encephalopathies, DEEs, Epilepsy, Drug Resistant Epilepsy, Intractable epilepsy, Nervous System Diseases, Genetic Diseases, Inborn
- Medical subject headings
- Drug Resistant Epilepsy, Epileptic Encephalopathy, Early Infantile, 4, Chromosome 15q, tetrasomy, Brain Diseases, Epilepsy, Nervous System Diseases, Genetic Diseases, Inborn
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FenfluramineDrug
Administration of fenfluramine. Fenfluramine treatment dose: Between 0.2 and 0.7 mg/kg/day if no concomitant Stiripentol (STP), maximum dose: 40 mg/day [or 0.5 mg/kg/day, maximum 30 mg/day, for subjects taking concomitant STP]. Dosing will be started with 0.1mg/day per one week, then 0.2mg/kg/day per one week, then as investigator clinical decision-making, up to 0.4, 0.6 or 0.7mg/kg/day, with a maximum of 0.2mg/kg/day escalation every week.
Visits: There will be four visits; (visit 1) screening; (visit 2) treatment initiation, +2 weeks; (visit 3, telematic) +8 weeks; (visit 4) +14 weeks.
| Study group | Role | What they receive |
|---|---|---|
| - Group 1A. | Experimental | Patients with genetic testing showing a pathogenic or likely pathogenic variant in main synaptopathy genes (SYNGAP1 and STXBP1) Receives: Drug: Fenfluramine |
| Group 1B. | Experimental | Patients with genetic testing showing a pathogenic or likely pathogenic inverted duplication of chromosome 15 [inv-dup (15)]. Receives: Drug: Fenfluramine |
| Group 1C. | Experimental | Patients with neuroimaging showing multifocal or bilateral malformations of cortical development. Receives: Drug: Fenfluramine |
| Group 2. | Experimental | Electroclinical diagnosis of Continuous Spikes and Waves during Sleep (CSWS) syndrome, with baseline video-EEG monitoring showing epileptiform activity occupying at least 50% of slow sleep tracing, after failing at least 3 antiseizure medications Receives: Drug: Fenfluramine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Seizure frequency.
Seizure diary.
Measured: 12 months.
Secondary outcomes (8)
Seizure severity.
Chalfont Seizure Severity Scale (CSSS).
Measured: 12 months.
Behaviour.
Behaviour Rating Inventory of Executive Function.
Measured: 12 months.
Gross motor function.
Gross Motor Function Measure (GMFM).
Measured: 12 months.
Sleep habits.
Parent-reported Children's Sleep Habits Questionnaire.
Measured: 12 months.
Global impression of change.
Caregiver Global Impression of Change.
Measured: 12 months.
Global impression of change.
Clinician Clinical Global Impression of Change - Improvement (CDD-CGI-I).
Measured: 12 months.
Quality of life and family impact.
PedsQL 4.0.
Measured: 12 months.
Epileptiform activity
12h video-EEG monitoring.
Measured: 12 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2022
- Study start20 Oct 2022
- Primary completion15 Dec 2024
- Study completion31 Dec 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory EpilepsyStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- 4 Group Assignment
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Ruber Internacional
- Sponsor type
- University, hospital or other
- Collaborators
- Zogenix, Inc.
- Responsible party
- Principal investigator, Antonio Gil-Nagel, Hospital Ruber Internacional
- Investigators
- Antonio Gil-Nagel, MD, PHD, Principal investigator, Hospital Ruber Internacional
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05232630
- Sponsor's protocol ID
- FENDEEP
- Acronym
- FENDEEP
- Status last verified
- Dec 2024
- First submitted
- 17 Jan 2022
- Last updated
- 29 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Fenfluramine for the Treatment of Different Types of Developmental and Epileptic Encephalopathies: a Pilot Trial Exploring Epileptic and Non-epileptic Outcomes
- ClinicalTrials.gov ID
- NCT05232630
- Acronym / sponsor ID
- FENDEEP / FENDEEP
- Conditions
- Refractory Epilepsy, SYNGAP1 Encephalopathy, STXBP1 Encephalopathy With Epilepsy, Inv Dup(15) Encephalopathy, Multifocal or Bilateral Malformations of Cortical Development, Continuous Spike and Waves During Slow Sleep
- Keywords
- refractory epilepsy, SYNGAP1, STXBP1, Inv Dup(15), developmental and epileptic encephalopathies, DEEs, Epilepsy, Drug Resistant Epilepsy
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Hospital Ruber InternacionalUniversity, hospital or other
- Collaborators
- Zogenix, Inc.
- Study start
- 20 Oct 2022 (actual)
- Primary completion
- 15 Dec 2024 (actual)
- Study completion
- 31 Dec 2024 (actual)
- First posted
- 10 Feb 2022 (actual)
- 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.
This study is a pilot non-controlled clinical trial with adjunctive fenfluramine for the treatment of five different types of developmental and epileptic encephalopathies (DEEs) focused on epileptic and "non-epileptic outcomes": SYNGAP1 and STXBP1 encephalopathies, inv-dup(15) encephalopathy, multifocal or bilateral malformations of cortical development, and continuous spikes and waves during sleep. The main goal is to assess changes in seizure frequency comparing before and after treatment with fenfluramine in five specific types of developmental and epileptic encephalopathies (DEEs). Secondary objectives of this study are the analysis of changes in seizure intensity and duration, and "non-epileptic outcomes" such as variations in cognitive activity, level of alertness, impulsivity/self-control, gait stability and other alterations that might be detected during the interview and physical examination.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- 4 Group Assignment
| Arm | Type | Receives |
|---|---|---|
| - Group 1A. | Experimental | Drug: FenfluraminePatients with genetic testing showing a pathogenic or likely pathogenic variant in main synaptopathy genes (SYNGAP1 and STXBP1) |
| Group 1B. | Experimental | Drug: FenfluraminePatients with genetic testing showing a pathogenic or likely pathogenic inverted duplication of chromosome 15 [inv-dup (15)]. |
| Group 1C. | Experimental | Drug: FenfluraminePatients with neuroimaging showing multifocal or bilateral malformations of cortical development. |
| Group 2. | Experimental | Drug: FenfluramineElectroclinical diagnosis of Continuous Spikes and Waves during Sleep (CSWS) syndrome, with baseline video-EEG monitoring showing epileptiform activity occupying at least 50% of slow sleep tracing, after failing at least 3 antiseizure medications |
Who may qualify
- Ages
- 2 to 35 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (0 listed)
Key exclusion criteria (16 listed)
- Subjects who meet any of the following exclusion criteria will not be enrolled into the study:
- Subject has a known hypersensitivity to fenfluramine or any of the excipients in the study medication.
- Subject has only non-motor seizures (such as absences), for group 1.
- Subject has pulmonary arterial hypertension.
- Subject has current or past history of cardiovascular or cerebrovascular disease.
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 |
|---|---|---|
| FenfluramineAdministration of fenfluramine. Fenfluramine treatment dose: Between 0.2 and 0.7 mg/kg/day if no concomitant Stiripentol (STP), maximum dose: 40 mg/day [or 0.5 mg/kg/day, maximum 30 mg/day, for subjects taking concomitant STP]. Dosing will be started with 0.1mg/day per one week, then 0.2mg/kg/day per one week, then as investigator clinical decision-making, up to 0.4, 0.6 or 0.7mg/kg/day, with a maximum of 0.2mg/kg/day escalation every week. Visits: There will be four visits; (visit 1) screening; (visit 2) treatment initiation, +2 weeks; (visit 3, telematic) +8 weeks; (visit 4) +14 weeks. | Drug | - Group 1A., Group 1B., Group 1C., Group 2. |
Primary outcome
Seizure frequency.
Time frame: 12 months.
Seizure diary.
8 secondary outcomes
Seizure severity.
Time frame: 12 months.
Behaviour.
Time frame: 12 months.
Gross motor function.
Time frame: 12 months.
Sleep habits.
Time frame: 12 months.
Global impression of change.
Time frame: 12 months.
Global impression of change.
Time frame: 12 months.
Quality of life and family impact.
Time frame: 12 months.
Epileptiform activity
Time frame: 12 months.
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 29 Sep 2026.
- Individual participant dataSharing planned: No
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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.
Antonio Gil-Nagel, MD, PHD principal investigator
Hospital Ruber Internacional
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Fenfluramine in people with Refractory Epilepsy and SYNGAP1 Encephalopathy, run by Hospital Ruber Internacional at 1 site in Spain.
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 0 inclusion and 16 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 29 Sep 2026. 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 Spain. 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
Seizure frequency. (time frame: 12 months.). 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 29 Sep 2026.