STXBP1 Encephalopathy With EpilepsyESCONCT06625112
A Multicentric European Study to Promote Clinical Trial Readiness for STXBP1-related Disorders
An observational study of STXBP1 Encephalopathy With Epilepsy, run by European STXBP1 Consortium at 1 site in Belgium.
Trial summary
STXBP1-related disorders (STXBP1-RD) are rare genetic neurodevelopmental disorders, caused by pathogenic variants in the gene STXBP1. The core clinical features of the disorder are developmental delay often leading to (severe) intellectual disability and seizures in most patients, although the phenotypic spectrum is… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- STXBP1 Encephalopathy With Epilepsy
- How many people
- 120 participants
- Where
- 1 siteBelgium
- Study dates
- 4 Nov 2025to 31 Oct 2034
- How long will I take part?
- 5 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with STXBP1 living in one of the 8 ESCO member countries( Belgium, Italy, Israel, Denmark, France, Spain, Netherlands, Germany) and has a (likely) pathogenic, disease-causing STXBP1 variant, according to t.
Who may be able to join
- participant has a (likely) pathogenic, disease-causing STXBP1 variant, according to the American College of Medical Genetics and Genomics (ACMG) criteria; or participant has a larger structural variant including the STXBP1 gene where STXBP1 is thought to be (one of) the culprit gene(s) causing the phenotype •written informed consent from study participant and/or legal guardian.
Who cannot join
- Exclusion criteria for the study are: none if the inclusion criteria are met.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Hannah Stamberger contact
Belgium1 site, 1 recruiting
- Recruiting
Universitair Ziekenhuis Antwerpen
Antwerp
Hannah Stamberger
About this study
STXBP1-related disorders (STXBP1-RD) are rare genetic neurodevelopmental disorders, caused by pathogenic variants in the gene STXBP1. The core clinical features of the disorder are developmental delay often leading to (severe) intellectual disability and seizures in most patients, although the phenotypic spectrum is variable. Behavioral problems and movement disorders are frequent comorbidities. STXBP1-RD are severe disorders with significant impact on the quality of life of the patients and their caregivers. At the moment, there is no cure for STXBP1-RD and treatment is largely limited to symptom control. Recent advances in the field of precision medicine and gene therapy have led to the identification of potential novel disease modifying therapies for STXBP1-RD that hold promise to reach clinical trials in the coming years. However, accurate and successful evaluation of such novel precision therapies in STXBP1-RD patients is challenging, given the rarity of the condition and the variable clinical spectrum. Furthermore, relevant clinical endpoints, taking into account the patients' and caregivers' perspective have not been identified to date.
In this European collaborative study, the investigators will prospectively follow patients with STXBP1-RD during different phases of life (infantile period, childhood and adolescence/adulthood). The study aims to better understand the natural history and the phenotypic spectrum of the disease including the identification of disease modifiers. It further aims to identify relevant clinical endpoints (what to treat?) and robust outcome measures and biomarkers (how to measure?) for future clinical trials. The study is performed in close collaboration with different STXBP1 patient-caregiver communities across Europe.
Read the detailed description
STXBP1-related disorders (STXBP1-RD) are a severe condition that heavily impact the life of affected individuals and their families. Core clinical features of STXBP1-RDs are seizures, developmental delay often leading to (severe) intellectual disability, movement disorders and behavioral problems [1]. The phenotypic spectrum and severity of the disease are variable. At the moment, there is no cure, nor disease modifying therapy for STXBP1-RD, and available treatments are largely symptomatic and mainly directed at seizure control. Furthermore, there is no defined standard of care for patients with STXBP1-RD, and unmet needs, as defined by patients and their caregivers, have not been systematically investigated. Potential disease-modifying therapies for STXBP1-RD hold the promise to be translated in the clinics in the coming years, but there are gaps to fill in order to prepare for successful, efficient, and rational evaluation of targeted therapies in STXBP1-RD. To accelerate the path towards a cure for STXB1P-RD, clinicians and researchers founded a European STXBP1 Consortium (ESCO). ESCO is committed to perform a large scale, pan-European natural history study in collaboration with STXBP1 Patient advocacy organizations (PAOs). This natural history study aims to provide an accurate description of STXBP1-RD trajectories, identify potential biomarkers, and incorporate the perspective of the patients and caregivers' community. The results of this comprehensive assessments will allow the evaluation of relevant endpoints and outcome measures, that will inform the design of future interventional studies with targeted therapies and provide an historical control group for such studies.
Primary objectives:
- Establishment of a European Registry of STXBP1-related disorders
- Characterization of the phenotypic spectrum of disease and to identify disease modifiers.
- Description of the longitudinal natural history of patients with STXBP1-RD for the purpose of historical control in interventional studies with disease-modifying therapies.
- Identification of relevant endpoints and outcome measures for clinical trials in STXBP1-RD.
Secondary objectives:
- Identification of disease biomarkers in STXBP1-RD for the purpose of complementing diagnosis, establishing prognosis, treatment decision support, and measuring treatment effects.
- Assessment of the disease burden on the quality of life and unmet needs, and establish the standard of care of STXBP1-RD.
A REDCap based Registry will include both retrospective and prospective data concerning demographics, genetics, and clinical features of individuals with STXBP1-RD. It will also form the basis of the prospective NHS.
The study is also composed of two phases: 1. Pilot Natural history study (pNHS), followed by 2. Extension Natural history (eNHS) study.
The investigators plan to enroll 50 individuals for the Pilot study and 70 additional individuals for the NHS study, including a total of 120 patients with STXBP1-RD of different ages.
The pNHS study is especially aimed at:
- assessing the sensitivity of the outcome measures in differentiating patients with different degrees of impairment in the respective disease domains, at different ages;
- assessing the sensitivity of the outcome measures to measure the change over time;
- assessing the burden of study participation for patients and their caregivers.
The pNHS study will have a duration of 12 months. Participants who completed the pNHS study will be enrolled in the following eNHS.
The eNHS study will have a 4-year duration.
- Conditions
- STXBP1 Encephalopathy With Epilepsy
- Keywords
- European, STXBP1, European STXBP1 Consortium, ESCO, STXBP1-RD, Syntaxin Binding Protein, epileptic encephalopathy, epilepsy, natural history study, registry
- Medical subject headings
- Epileptic Encephalopathy, Early Infantile, 4, Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Natural history study participants | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in clinical assessment percentiles over time.
The primary analysis will include all participants who meet the inclusion and exclusion criteria and complete the first visit. For each participant, the percentage of correct responses on clinical assessments will be recorded. Variations in percentile scores over the study period will be examined using a linear mixed-effects model, allowing for the repeated observations collected from each participant.
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 posted3 Oct 2024
- Study start4 Nov 2025
- Primary completion31 Oct 2029 (estimated)
- Study completion31 Oct 2034 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for STXBP1 Encephalopathy With 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
- Observational
- Observational model
- Case only
- Time perspective
- Other
- Enrolment
- 120 participants (estimated)
- Target duration
- 5 Years
Sponsor and investigators
- Lead sponsor
- European STXBP1 Consortium
- Sponsor type
- Research network
- Collaborators
- Filadelfia Epilepsy Hospital, University Hospital Heidelberg, University Hospital, Antwerp, Istituto Giannina Gaslini, Genoa, Italy, Hospital Sant Joan de Deu, Amsterdam UMC, location VUmc, Sheba Medical Center, Aix Marseille Université, Hospital Ruber Internacional
- Responsible party
- Principal investigator, Kelsey Ax, European STXBP1 Consortium
- Investigators
- Matthijs Verhage, Study chair, Amsterdam UMCHannah Stamberger, Principal investigator, University Hospital, AntwerpGanna Balagura, Principal investigator, Università degli Studi di GenovaAndrea Soto-Padilla, Study director, Amsterdam UMC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06625112
- Sponsor's protocol ID
- ESCO-STXBP1-2024-001
- Acronym
- ESCO
- Status last verified
- Feb 2026
- First submitted
- 4 Sep 2024
- Last updated
- 6 Feb 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicentric European Study to Promote Clinical Trial Readiness for STXBP1-related Disorders
- ClinicalTrials.gov ID
- NCT06625112
- Acronym / sponsor ID
- ESCO / ESCO-STXBP1-2024-001
- Conditions
- STXBP1 Encephalopathy With Epilepsy
- Keywords
- European, STXBP1, European STXBP1 Consortium, ESCO, STXBP1-RD, Syntaxin Binding Protein, epileptic encephalopathy, epilepsy
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- European STXBP1 ConsortiumResearch network
- Collaborators
- Filadelfia Epilepsy Hospital, University Hospital Heidelberg, University Hospital, Antwerp, Istituto Giannina Gaslini, Genoa, Italy, Hospital Sant Joan de Deu, Amsterdam UMC, location VUmc, Sheba Medical Center, Aix Marseille Université, Hospital Ruber Internacional
- Study start
- 4 Nov 2025 (actual)
- Primary completion
- 31 Oct 2029 (estimated)
- Study completion
- 31 Oct 2034 (estimated)
- First posted
- 3 Oct 2024 (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.
STXBP1-related disorders (STXBP1-RD) are rare genetic neurodevelopmental disorders, caused by pathogenic variants in the gene STXBP1. The core clinical features of the disorder are developmental delay often leading to (severe) intellectual disability and seizures in most patients, although the phenotypic spectrum is variable. Behavioral problems and movement disorders are frequent comorbidities. STXBP1-RD are severe disorders with significant impact on the quality of life of the patients and their caregivers. At the moment, there is no cure for STXBP1-RD and treatment is largely limited to symptom control. Recent advances in the field of precision medicine and gene therapy have led to the identification of potential novel disease modifying therapies for STXBP1-RD that hold promise to reach clinical trials in the coming years. However, accurate and successful evaluation of such novel precision therapies in STXBP1-RD patients is challenging, given the rarity of the condition and the variable clinical spectrum. Furthermore, relevant clinical endpoints, taking into account the patients' and caregivers' perspective have not been identified to date.
In this European collaborative study, the investigators will prospectively follow patients with STXBP1-RD during different phases of life (infantile period, childhood and adolescence/adulthood). The study aims to better understand the natural history and the phenotypic spectrum of the disease including the identification of disease modifiers. It further aims to identify relevant clinical endpoints (what to treat?) and robust outcome measures and biomarkers (how to measure?) for future clinical trials. The study is performed in close collaboration with different STXBP1 patient-caregiver communities across Europe.
Detailed description
STXBP1-related disorders (STXBP1-RD) are a severe condition that heavily impact the life of affected individuals and their families. Core clinical features of STXBP1-RDs are seizures, developmental delay often leading to (severe) intellectual disability, movement disorders and behavioral problems [1]. The phenotypic spectrum and severity of the disease are variable. At the moment, there is no cure, nor disease modifying therapy for STXBP1-RD, and available treatments are largely symptomatic and mainly directed at seizure control. Furthermore, there is no defined standard of care for patients with STXBP1-RD, and unmet needs, as defined by patients and their caregivers, have not been systematically investigated. Potential disease-modifying therapies for STXBP1-RD hold the promise to be translated in the clinics in the coming years, but there are gaps to fill in order to prepare for successful, efficient, and rational evaluation of targeted therapies in STXBP1-RD. To accelerate the path towards a cure for STXB1P-RD, clinicians and researchers founded a European STXBP1 Consortium (ESCO). ESCO is committed to perform a large scale, pan-European natural history study in collaboration with STXBP1 Patient advocacy organizations (PAOs). This natural history study aims to provide an accurate description of STXBP1-RD trajectories, identify potential biomarkers, and incorporate the perspective of the patients and caregivers' community. The results of this comprehensive assessments will allow the evaluation of relevant endpoints and outcome measures, that will inform the design of future interventional studies with targeted therapies and provide an historical control group for such studies.
Primary objectives:
- Establishment of a European Registry of STXBP1-related disorders
- Characterization of the phenotypic spectrum of disease and to identify disease modifiers.
- Description of the longitudinal natural history of patients with STXBP1-RD for the purpose of historical control in interventional studies with disease-modifying therapies.
- Identification of relevant endpoints and outcome measures for clinical trials in STXBP1-RD.
Secondary objectives:
- Identification of disease biomarkers in STXBP1-RD for the purpose of complementing diagnosis, establishing prognosis, treatment decision support, and measuring treatment effects.
- Assessment of the disease burden on the quality of life and unmet needs, and establish the standard of care of STXBP1-RD.
A REDCap based Registry will include both retrospective and prospective data concerning demographics, genetics, and clinical features of individuals with STXBP1-RD. It will also form the basis of the prospective NHS.
The study is also composed of two phases: 1. Pilot Natural history study (pNHS), followed by 2. Extension Natural history (eNHS) study.
The investigators plan to enroll 50 individuals for the Pilot study and 70 additional individuals for the NHS study, including a total of 120 patients with STXBP1-RD of different ages.
The pNHS study is especially aimed at:
- assessing the sensitivity of the outcome measures in differentiating patients with different degrees of impairment in the respective disease domains, at different ages;
- assessing the sensitivity of the outcome measures to measure the change over time;
- assessing the burden of study participation for patients and their caregivers.
The pNHS study will have a duration of 12 months. Participants who completed the pNHS study will be enrolled in the following eNHS.
The eNHS study will have a 4-year duration.
Study design
- Observational model
- Case only
- Time perspective
- Other
- Target follow-up
- 5 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Natural history study participants | – | – |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with STXBP1 living in one of the 8 ESCO member countries( Belgium, Italy, Israel, Denmark, France, Spain, Netherlands, Germany) and has a (likely) pathogenic, disease-causing STXBP1 variant, according to t.
Key inclusion criteria (1 listed)
- participant has a (likely) pathogenic, disease-causing STXBP1 variant, according to the American College of Medical Genetics and Genomics (ACMG) criteria; or participant has a larger structural variant including the STXBP1 gene where STXBP1 is thought to be (one of) the culprit gene(s) causing the phenotype •written informed consent from study participant and/or legal guardian.
Key exclusion criteria (1 listed)
- Exclusion criteria for the study are: none if the inclusion criteria are met.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Changes in clinical assessment percentiles over time.
Time frame: 12 months
The primary analysis will include all participants who meet the inclusion and exclusion criteria and complete the first visit. For each participant, the percentage of correct responses on clinical assessments will be recorded. Variations in percentile scores over the study period will be examined using a linear mixed-effects model, allowing for the repeated observations collected from each participant.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2026.
- ESCO websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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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.
Hannah Stamberger contact
Matthijs Verhage study chair
Amsterdam UMC
Hannah Stamberger principal investigator
University Hospital, Antwerp
Ganna Balagura principal investigator
Università degli Studi di Genova
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of STXBP1 Encephalopathy With Epilepsy, run by European STXBP1 Consortium at 1 site in Belgium.
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 1 inclusion and 1 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: looking for participants now, as of the sponsor's last update on 6 Feb 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 Belgium. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelsey Ax (+31 205981347, k.a.ax@vu.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in clinical assessment percentiles over time. (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 6 Feb 2026; AzTrials last refreshed its copy on 7 Nov 2026.