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Not yet recruitingNCT07801404TEMBO-DSUpdated Sep 3, 2026

Biomarkers of Neurodegeneration, Synaptic Plasticity and Neuroinflammation in Dravet Syndrome

An observational study in Dravet Syndrome (DS), sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS. Not yet recruiting at 9 sites in Italy. Per ClinicalTrials.gov, last updated 2026-09-03.

Sponsored by Fondazione Policlinico Universitario Agostino Gemelli IRCCS · Observational

Study type
Observational
Model
Case-control
Time perspective
Prospective
Enrollment
90
Sex
All
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Study summary

Dravet syndrome (DS) is a developmental and epileptic encephalopathy, usually caused by de novo pathogenic SCN1A variants, characterized by early-onset prolonged febrile seizures, subsequent drug-resistant polymorphic epilepsy, developmental impairment, and, in some patients, progressive motor, cognitive and behavioral decline. Despite the expanding therapeutic landscape, objective biomarkers for disease stratification, monitoring and treatment response are lacking. Blood-based markers of neurodegeneration, synaptic plasticity and neuroinflammation are promising candidates because they are minimally invasive and may capture biological processes involved in disease progression.

TEMBO-DS is a prospective multicenter observational pilot study enrolling 60 individuals with DS and 30 age- and sex-matched healthy controls. DS participants will carry pathogenic or likely pathogenic SCN1A variants and fulfill ILAE clinical criteria, with no age limits. Individuals with epileptic spasms, SCN1A gain-of-function encephalopathy, structural causes of epilepsy, or systemic, oncological, autoimmune or neurodegenerative conditions potentially affecting biomarker levels will be excluded.

At baseline, demographic and clinical variables will be collected, including age at seizure onset, seizure type and frequency, status epilepticus, SCN1A variant type, cognitive, motor, behavioral and sleep profiles, comorbidities and ongoing treatments. Blood samples obtained during routine clinical sampling will be analyzed for biomarkers of neurodegeneration and glial injury (NfL, GFAP, tau-related markers), synaptic plasticity (BDNF) and neuroinflammation. In a subgroup of DS participants, clinical assessment and blood sampling will be repeated after approximately 12 months.

The study will assess whether biomarker levels differ between DS and controls and whether they correlate with clinically relevant measures of disease severity and longitudinal change. Particular emphasis will be placed on the relationship between NfL and Vineland adaptive functioning, including their changes over 12 months and the effect of treatment modifications. Group comparisons, correlation analyses and longitudinal mixed-effects models will be used, with adjustment for relevant covariates and multiple testing.

The study is expected to identify one or more blood-based biomarkers, or biomarker combinations, associated with DS, disease severity and clinical evolution. These findings may provide objective measures for future natural-history studies and therapeutic trials, including the assessment of non-seizure outcomes.

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Conditions studied

  • Dravet Syndrome (DS)

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Who can participate

Ages eligible
Child (0–17), Adult (18–64), Older adult (65+)
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

Subjects with a diagnosis of Dravet Syndrome (disease onset between 1 and 20 months of life, recurrent febrile and afebrile hemiclonic seizures, as well as focal seizures evolving to bilateral tonic-clonic seizures and/or generalized tonic-clonic seizures) without age limits, and control subjects matched for sex and age, as per the inclusion criteria.

Inclusion criteria

Subjects with Dravet Syndrome (DS):

  • Subjects carrying SCN1A gene variants classified as pathogenic or likely pathogenic (classes IV and V), in association with the clinical criteria defined by the ILAE (Zuberi, 2022), including: disease onset between 1 and 20 months of life, recurrent febrile and afebrile hemiclonic seizures, as well as focal seizures evolving to bilateral tonic-clonic seizures and/or generalized tonic-clonic seizures, will be included in the study.
  • No age limits are planned for recruitment. In order to ensure adequate representation of the different age groups, at least one third of enrolled subjects will be younger than 10 years and at least one third older than 18 years.
  • Informed consent signed by the parent/guardian or by the patient themself if an adult. For adult patients with intellectual disability such as to impair the capacity to consent to participation, informed consent will be obtained from the guardian/legal representative.
  • Informed assent signed by the minor.

Healthy controls (HC):

  • Subjects without neurological disorders for whom a blood sample is planned for screening or for clinical questions not conflicting with the exclusion criteria, matched for age and sex to the DS group (±2 years).
  • Informed consent signed by the parent/guardian or by the patient themself if an adult.
  • Informed assent signed by the minor.

Exclusion criteria

Exclusion Criteria:

  • Subjects with a history of epileptic spasms, early-onset epileptic encephalopathy associated with gain-of-function SCN1A variants, as well as subjects with brain MRI findings indicative of a focal cause of epilepsy.
  • Patients affected by systemic diseases, including autoimmune or oncological conditions, and by neurodegenerative diseases potentially able to interfere with the levels of the biomarkers under study.
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Study design

Observational model
Case-control
Time perspective
Prospective
Enrollment
90 participants (estimated)
Patient registry
No

Groups and cohorts

  • Dravet Syndrome

    Patients with SCN1A-related Dravet Syndrome defined according to ILAE 2022 criteria and with pathogenic or likely pathogenic SCN1A variants

  • Healthy controls

    Subjects without neurological disorders for whom a blood sample is planned for screening or for clinical questions not conflicting with the exclusion criteria matched for age and sex to the DS group (±2 years)

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What researchers measure

Primary outcomes

  1. Identify promising biomarkers in DS at T0

    The purpose is to verify whether biomarkers of neurodegeneration, synaptic plasticity and neuroinflammation are altered in DS compared with controls matched for sex and age, and whether they correlate with clinical variables at baseline (e.g. age at onset, disease duration, history of status epilepticus, mutation type, degree of intellectual disability, degree of motor and behavioral impairment).

    Time frame: 1 day

  2. Verify the natural course of biomarkers over time and the correlation with factors occurring between T0 and T1

    After 12 months, clinical variables and biological samples will again be collected. The objective is to verify how the processes of neurodegeneration, synaptic plasticity and neuroinflammation change with disease evolution between T0 and T1. In the analysis of factors occurring between T0 and T1, both changes in symptoms and treatment changes will be considered.

    Time frame: 12 months

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Study locations

9 sites
  • SOD Neuropsichiatria Infantile, Dipartimento Materno Infantile, Azienda Ospedaliero Universitaria delle Marche
    Ancona, Italy
  • UOC Neurologia Pediatrica, Dipartimento di Neuroscienze, Azienda Ospedaliero-Universitaria Meyer IRCSS
    Florence, Italy
  • UOC Neurologia pediatrica e Malattie Muscolari, Dipartimento di Neuroscienze, Riabilitazione, Oftalmologia, Genetica e Scienze Materno-Infantili, Università degli Studi di Genova, Istituto Giannina Gaslini
    Genova, Italy
  • UOC Neuropsichiatria Infantile, Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina, Messina
    Messina, Italy
  • UOC Neuropsichiatria Infantile, Dipartimento Neuroscienze Pediatriche, IRCCS Istituto Neurologico Carlo Besta
    Milan, Italy
  • UOC Neurologia dell'epilessia, Dipartimento di Neuroscienze, Ospedale Pediatrico Bambino Gesù IRCCS
    Roma, Italy
  • UOC Neuropsichiatria Infantile, Dipartimento Neuroscienze Umane, Sapienza Università di Roma
    Rome, Italy
  • UOC Pediatria, Dipartimento Scienze Ostetriche, Ginecologiche e Pediatriche, Azienda Ospedaliero-Universitaria Sant'Andrea, Università Sapienza
    Rome, Italy
  • UOC Neuropsichiatria Infantile, Dipartimento Materno Infantile, Azienda Ospedaliera Universitaria Integrata
    Verona, Italy
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Registry details

Key details

Study ID
NCT07801404
Lead sponsor
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Responsible party
Sponsor
First posted
Sep 3, 2026
Start date
Sep 15, 2026 (estimated)
Primary completion
Mar 15, 2028 (estimated)
Completion
Sep 15, 2028 (estimated)
Last update
Sep 3, 2026

Study contacts

Domenica Immacolata Battaglia
Contact
domenicaimmacolata.battaglia@policlinicogemelli.it
+39 0630156239
Domenica Immacolata Battaglia
principal investigator · Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Oversight

FDA-regulated drug
No
FDA-regulated device
No
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