Fenfluramine for the Treatment of Different Types of Developmental and Epileptic Encephalopathies: a Pilot Trial Exploring Epileptic and Non-epileptic Outcomes

Phase 4

Recruiting

• Conditions: SYNGAP1 Encephalopathy; Refractory Epilepsy; STXBP1 Encephalopathy With Epilepsy; Inv Dup(15) Encephalopathy; Multifocal or Bilateral Malformations of Cortical Development; Continuous Spike and Waves During Slow Sleep
• Interventions: Drug: Fenfluramine

• Registration Number: NCT05232630
• Lead Sponsor: Hospital Ruber Internacional

Brief 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 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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-01-17
• Study First Submitted QC: 2022-01-31
• Study First Posted: 2022-02-10
• Study Start: 2022-10-20
• Status Verified: 2024-02
• Last Update Submitted: 2024-02-26
• Last Update Posted: 2024-02-28
• Primary Completion: 2025-02-20
• Study Completion: 2025-06-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
- Group 1A.	Fenfluramine	Patients with genetic testing showing a pathogenic or likely pathogenic variant in main synaptopathy genes (SYNGAP1 and STXBP1)
Group 1B.	Fenfluramine	Patients with genetic testing showing a pathogenic or likely pathogenic inverted duplication of chromosome 15 \[inv-dup (15)\].
Group 1C.	Fenfluramine	Patients with neuroimaging showing multifocal or bilateral malformations of cortical development.
Group 2.	Fenfluramine	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

Primary Outcome Measures

Name	Time	Method
Seizure frequency.	12 months.	Seizure diary.

Secondary Outcome Measures

Name	Time	Method
Behaviour.	12 months.	Behaviour Rating Inventory of Executive Function.
Gross motor function.	12 months.	Gross Motor Function Measure (GMFM).
Seizure severity.	12 months.	Chalfont Seizure Severity Scale (CSSS).
Sleep habits.	12 months.	Parent-reported Children's Sleep Habits Questionnaire.
Global impression of change.	12 months.	Clinician Clinical Global Impression of Change - Improvement (CDD-CGI-I).
Quality of life and family impact.	12 months.	PedsQL 4.0.
Epileptiform activity	12 months.	12h video-EEG monitoring.

Trial Locations

Locations (1)

Hospital Ruber Internacional; 🇪🇸 Madrid, Spain