Tracking development, seizures, and biomarkers over four years in children and young adults with SCN1A-related Dravet syndrome

Longitudinal Study of Phenotypic and Developmental Severity in Patients With Dravet Syndrome With SCN1A Gene Mutation

This project will follow children and young people with SCN1A-related Dravet syndrome for four years to see how their development, seizure patterns, and blood metabolite markers change over time.

Quick facts

• Study type: Observational
• Enrollment: 50 (estimated)
• Ages: 6 Months to 21 Years
• Sex: All
• Sponsor: Assistance Publique - Hôpitaux de Paris (Academic / other)
• Locations: 1 site (Paris, Ap-hp / DRCI)
• Trial ID: NCT07251673 on ClinicalTrials.gov

What this trial studies

This is a four-year prospective natural-history cohort of patients aged 6 months to 21 years with a confirmed pathogenic or likely pathogenic SCN1A variant. Participants undergo a baseline visit with detailed clinical history and standardized assessments (Vineland-3, GMFM-66, CGI-S, Bayley-IV where appropriate) and an extra blood sample for metabolomics including serum GABA, then annual follow-up visits to document clinical course and repeat key measures. Eligibility requires seizure onset between 3 and 15 months, prior normal development, and current treatment with at least one listed anti-epileptic drug. The study aims to define neurodevelopmental trajectories and explore metabolomic biomarkers that correlate with clinical outcomes.

Who should consider this trial

Good fit: Ideal candidates are patients aged 6 months to 21 years with a confirmed pathogenic or likely pathogenic SCN1A variant, seizure onset between 3 and 15 months, prior normal development, and currently taking at least one of the specified anti-epileptic drugs.

Not a fit: Patients without an SCN1A pathogenic variant, those with SCN1A copy number changes affecting other genes, people older than 21, or those seeking direct therapeutic benefit from participation are unlikely to gain clinical benefit from this observational study.

Why it matters

Potential benefit: If successful, the work could help clinicians predict developmental and seizure trajectories and identify blood biomarkers to guide future personalized treatments and trial design.

How similar studies have performed: Previous natural-history studies of SCN1A-positive Dravet syndrome have provided useful short-term or age-limited data, but long-term prospective cohorts are limited and metabolomic biomarker work remains exploratory.

Eligibility criteria

Inclusion Criteria:

* The patient or his/her legal representative must be able to give informed consent for participation in the study.
* The participant or legal representative are able (in the opinion of the investigator) to comply with the research protocol.
* Patient (male/female) between 6 months and 21 years of age inclusive at the time of consent.
* The patient has a confirmed pathogenic or probably pathogenic variant of the SCN1A gene demonstrated by a genetic test.
* The patient had normal development prior to the onset of the first seizure.
* The patient had an onset of epileptic seizures between the ages of 3 and 15 months inclusive.
* The patient is receiving at least one of the following anti-epileptic drugs prior to consent: brivaracetam, clobazam, cannabidiol, fenfluramine, levetiracetam, sodium valproate, stiripentol, topiramate

Exclusion Criteria:

* The patient has a copy number variation of the SCN1A gene affecting other genes, including a microdeletion of SCN1A.
* The patient has a mutation in the SCN1A gene on both alleles.
* The patient has a known or clinically suspected pathogenic mutation in a gene associated with epilepsy other than the SCN1A gene.
* The patient has a concomitant genetic mutation or clinical comorbidity deemed likely to disrupt the typical phenotype of Dravet syndrome.
* The patient has a known gain-of-function mutation, defined by functional studies, including p.Thr226Met.
* The patient has a history of neurodevelopmental abnormality prior to the onset of seizures, based on the medical record.
* The patient has been seizure free for a period of one year prior to informed consent.
* The patient has, at any time, taken antiepileptic drugs with a worsening effect for 6 consecutive weeks or more, including: carbamazepine, eslicarbazepine, lacosamide, lamotrigine, oxcarbazepine, phenytoin (chronic oral administration), tiagabine and vigabatrin.
* The patient has already received innovative therapies such as antisense ologonucleotides, gene therapy or cell therapy.
* The patient has a structural abnormality on brain imaging (MRI or CT scan) which the principal investigator considers to be an epileptogenic lesion.

Where this trial is running

Paris, Ap-hp / DRCI

• Robert Debré Hospital — Paris, Ap-hp / DRCI, France (Recruiting)

Study contacts

• Principal investigator: Stéphane Auvin, MD, PhD — Assistance Publique - Hôpitaux de Paris
• Study coordinator: Stéphane Auvin, MD, PhD

Conditions Dravet Syndrome; Dravet syndrom; epilepsy