Biomarkers of Neurodegeneration, Synaptic Plasticity and Neuroinflammation in Dravet Syndrome (TEMBO-DS)

August 28, 2026 updated by: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
90

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • Italy
      • Ancona, Italy
        • SOD Neuropsichiatria Infantile, Dipartimento Materno Infantile, Azienda Ospedaliero Universitaria delle Marche
        • Contact:
      • Florence, Italy
        • UOC Neurologia Pediatrica, Dipartimento di Neuroscienze, Azienda Ospedaliero-Universitaria Meyer IRCSS
        • Contact:
      • Genova, 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
        • Contact:
      • Messina, Italy
        • UOC Neuropsichiatria Infantile, Azienda Ospedaliera Universitaria Policlinico G. Martino, Università di Messina, Messina
        • Contact:
      • Milan, Italy
        • UOC Neuropsichiatria Infantile, Dipartimento Neuroscienze Pediatriche, IRCCS Istituto Neurologico Carlo Besta
        • Contact:
      • Roma, Italy
        • UOC Neurologia dell'epilessia, Dipartimento di Neuroscienze, Ospedale Pediatrico Bambino Gesù IRCCS
        • Contact:
      • Rome, Italy
        • UOC Neuropsichiatria Infantile, Dipartimento Neuroscienze Umane, Sapienza Università di Roma
        • Contact:
      • Rome, Italy
        • UOC Pediatria, Dipartimento Scienze Ostetriche, Ginecologiche e Pediatriche, Azienda Ospedaliero-Universitaria Sant'Andrea, Università Sapienza
        • Contact:
      • Verona, Italy
        • UOC Neuropsichiatria Infantile, Dipartimento Materno Infantile, Azienda Ospedaliera Universitaria Integrata
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

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.

Description

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:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
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)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Identify promising biomarkers in DS at T0
Time Frame: 1 day
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).
1 day
Verify the natural course of biomarkers over time and the correlation with factors occurring between T0 and T1
Time Frame: 12 months
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.
12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Domenica Immacolata Battaglia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 15, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 15, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 15, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 28, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 3, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 28, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
August 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 27582

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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