MedPath

STXBP1 and SYNGAP1 Related Disorders Natural History Study

Recruiting
Conditions
SYNGAP1-Related Intellectual Disability
Genetic Disease
STXBP1 Encephalopathy With Epilepsy
Interventions
Other: Non-interventional study
Registration Number
NCT06555965
Lead Sponsor
Children's Hospital of Philadelphia
Brief Summary

The purpose of this study is to find out more about STXBP1 and SYNGAP1 related disorders. The information gathered by this study will be used to prepare for clinical treatment trials. The primary objective of the study is to better define and outline the clinical spectrum of STXBP1 and SYNGAP1 through detailed developmental, seizure, and quality of life assessments as an extension of routine clinical care.

Detailed Description

STXBP1 and SYNGAP1 related disorders are genetic disorders that cause differences in the synaptic transmission of the brain. Disease-causing variants in these genes lead to a spectrum of developmental delay that is most often severe, epileptic encephalopathies, and complex behavioral and psychiatric disorders. As there are multiple targeted therapies in development for these conditions, there is an urgent need to push forward a prospective natural history study in order to define specific disease outcomes in these genetic conditions.

Participation may last up to five years and will involve up to 10 study visits. Detailed questions about health and medical history, physical exams, electrographic encephalogram (EEG) or quantitative EEG (qEEG) and some age-appropriate assessments of neurodevelopmental and behavioral function are some of the study procedures. Study procedures will occur during regularly scheduled clinic visits. Participants will undergo assessments at baseline visit and semi-annually (every 6 months for 2-5 years).

The primary objective of the study is to better define and outline the clinical spectrum of STXBP1 and SYNGAP1 through detailed developmental, seizure, and quality of life assessments as an extension of routine clinical care.

The secondary objectives of the study are listed below:

* To evaluate changes in neurodevelopmental and behavioral parameters as assessed by instruments appropriate to the study population.

* To assess the burden of disease by quality-of-life instruments appropriate to the study population.

* To assess the burden of performing multiple outcome measures and scales on the caregiver, participant, and clinical personnel.

* To assess health care resource utilization

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
400
Inclusion Criteria
  • Male or female of any age.
  • Presence of a STXBP1 or SYNGAP1 gene mutation. The variant in STXBP1 or SYNGAP1 must be classified as causative based on clinical and variant classification criteria. Historical documentation is sufficient to support eligibility for the study. Confirmatory testing will be obtained, if necessary, at baseline and performed by a CLIA certified laboratory.
Exclusion Criteria
  • The presence of a confirmed mutation in a gene other than STXBP1 or SYNGAP1 that is known to contribute to a neurodevelopmental disability. This includes full gene deletions of STXBP1 or SYNGAP1 that include other genes beyond STXBP1 or SYNGAP1.
  • The presence of a significant non-STXBP1-RD or non-SYNGAP1-RD related central nervous impairment/behavioral disturbance that would confound the scientific rigor or interpretation of results of the study.
  • History of intraventricular hemorrhage, structural brain deficit or congenital heart disease
  • The presence of a clinical comorbidity deemed by the investigator to potentially confound the typical presentation of STXBP1-RD or SYNGAP1-RD.
  • Pregnant women or females of age of menarche who are found to be pregnant upon urine pregnancy testing.

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
SYNGAP1 cohortNon-interventional study-
STXBP1 cohortNon-interventional study-
Primary Outcome Measures
NameTimeMethod
Changes in percentiles recorded on clinical assessments over timeEvery 6 months upto 5 years

The primary analysis will include all subjects meeting all inclusion and exclusion criteria and completing Visit 1. For each subject, the percentage of items performed correctly on the clinical assessments will be recorded. Changes in percentiles over time will be analyzed using a linear mixed effects model, to account for repeated measures for each patient.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (5)

Stanford Medicine Children's Health

🇺🇸

Palo Alto, California, United States

Children's Hospital Colorado

🇺🇸

Aurora, Colorado, United States

Weill Cornell Medicine

🇺🇸

New York, New York, United States

The Children's Hospital of Philadelphia

🇺🇸

Philadelphia, Pennsylvania, United States

Texas Children's Hospital

🇺🇸

Houston, Texas, United States

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