A Multicentric European Study to Promote Clinical Trial Readiness for STXBP1-related Disorders

NCT06625112 | Recruiting

• 1 other identifier: ESCO-STXBP1-2024-001
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

STXBP1 Encephalopathy With Epilepsy

Keywords

European; STXBP1; European STXBP1 Consortium; ESCO; STXBP1-RD; Syntaxin Binding Protein; epileptic encephalopathy; epilepsy; natural history study; registry

Outcome Measures

Primary Outcomes (1)

• 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.

  12 months

Study Arms (1)

Natural history study participants

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.

Sponsors & Collaborators

• European STXBP1 Consortium: lead
• Filadelfia Epilepsy Hospital: collaborator
• University Hospital Heidelberg: collaborator
• University Hospital, Antwerp: collaborator
• Istituto Giannina Gaslini, Genoa, Italy: collaborator
• Hospital Sant Joan de Deu: collaborator
• Amsterdam UMC, location VUmc: collaborator
• Sheba Medical Center: collaborator
• Aix Marseille Université: collaborator
• Hospital Ruber Internacional: collaborator

Study Sites (1)

Universitair Ziekenhuis Antwerpen

Antwerp, Belgium

RECRUITING

Related Links

• ESCO website

Biospecimen

Retention: SAMPLES WITH DNA

The participant / legal representative can choose and consent to donate optional samples. * Plasma/serum * Urine * DNA * Peripheral Blood Mononuclear Cell (PBMC) * Cerebrospinal fluid (CSF)

MeSH Terms

Conditions

Epileptic Encephalopathy, Early Infantile, 4; Epilepsy

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Matthijs Verhage

  Amsterdam UMC

  STUDY CHAIR

• Hannah Stamberger

  University Hospital, Antwerp

  PRINCIPAL INVESTIGATOR

• Ganna Balagura

  Università degli Studi di Genova

  PRINCIPAL INVESTIGATOR

• Andrea Soto-Padilla

  Amsterdam UMC

  STUDY DIRECTOR

Central Study Contacts

Kelsey Ax

CONTACT

+31 205981347; k.a.ax@vu.nl

Hannah Stamberger

CONTACT

Hannah.Stamberger@uantwerpen.vib.be

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: OTHER
• Target Duration: 5 Years
• Sponsor Type: NETWORK
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Manager

Study Record Dates

• First Submitted: September 4, 2024
• First Posted: October 3, 2024
• Study Start: November 4, 2025
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2034
• Last Updated: February 6, 2026

Record last verified: 2026-02

Locations

BE (1)