STXBP1 and SYNGAP1 Related Disorders Natural History Study

NCT ID: NCT06555965

Last Updated: 2025-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

600 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-08-30

Study Completion Date

2028-12-30

Brief Summary

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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

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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

Conditions

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Genetic Disease STXBP1 Encephalopathy With Epilepsy SYNGAP1-Related Intellectual Disability

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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STXBP1 cohort

Non-interventional study

Intervention Type OTHER

There is no planned intervention in this study

SYNGAP1 cohort

Non-interventional study

Intervention Type OTHER

There is no planned intervention in this study

Interventions

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Non-interventional study

There is no planned intervention in this study

Intervention Type OTHER

Eligibility Criteria

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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.
Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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STXBP1 Foundation

UNKNOWN

Sponsor Role collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ingo Helbig, MD

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

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Stanford Medicine Children's Health

Palo Alto, California, United States

Site Status RECRUITING

Children's Hospital Colorado

Aurora, Colorado, United States

Site Status RECRUITING

Weill Cornell Medicine

New York, New York, United States

Site Status RECRUITING

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Joeylynn Nolan, RRT NPS AE-C

Role: CONTACT

2674411813

Victoria Chisari, BA, NS

Role: CONTACT

Facility Contacts

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Swetapadma Patnaik

Role: primary

Megan Stringfellow

Role: primary

Millie Stone

Role: primary

Joeylynn Nolan

Role: primary

Ekaterina Sanchez Romero

Role: primary

References

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Xian J, Parthasarathy S, Ruggiero SM, Balagura G, Fitch E, Helbig K, Gan J, Ganesan S, Kaufman MC, Ellis CA, Lewis-Smith D, Galer P, Cunningham K, O'Brien M, Cosico M, Baker K, Darling A, Veiga de Goes F, El Achkar CM, Doering JH, Furia F, Garcia-Cazorla A, Gardella E, Geertjens L, Klein C, Kolesnik-Taylor A, Lammertse H, Lee J, Mackie A, Misra-Isrie M, Olson H, Sexton E, Sheidley B, Smith L, Sotero L, Stamberger H, Syrbe S, Thalwitzer KM, van Berkel A, van Haelst M, Yuskaitis C, Weckhuysen S, Prosser B, Son Rigby C, Demarest S, Pierce S, Zhang Y, Moller RS, Bruining H, Poduri A, Zara F, Verhage M, Striano P, Helbig I. Assessing the landscape of STXBP1-related disorders in 534 individuals. Brain. 2022 Jun 3;145(5):1668-1683. doi: 10.1093/brain/awab327.

Reference Type BACKGROUND
PMID: 35190816 (View on PubMed)

Yang P, Broadbent R, Prasad C, Levin S, Goobie S, Knoll JH, Prasad AN. De novo STXBP1 Mutations in Two Patients With Developmental Delay With or Without Epileptic Seizures. Front Neurol. 2021 Dec 24;12:804078. doi: 10.3389/fneur.2021.804078. eCollection 2021.

Reference Type BACKGROUND
PMID: 35002943 (View on PubMed)

Wang HH, Liao HF, Hsieh CL. Reliability, sensitivity to change, and responsiveness of the peabody developmental motor scales-second edition for children with cerebral palsy. Phys Ther. 2006 Oct;86(10):1351-9. doi: 10.2522/ptj.20050259.

Reference Type BACKGROUND
PMID: 17012639 (View on PubMed)

Demarest S, Pestana-Knight EM, Olson HE, Downs J, Marsh ED, Kaufmann WE, Partridge CA, Leonard H, Gwadry-Sridhar F, Frame KE, Cross JH, Chin RFM, Parikh S, Panzer A, Weisenberg J, Utley K, Jaksha A, Amin S, Khwaja O, Devinsky O, Neul JL, Percy AK, Benke TA. Severity Assessment in CDKL5 Deficiency Disorder. Pediatr Neurol. 2019 Aug;97:38-42. doi: 10.1016/j.pediatrneurol.2019.03.017. Epub 2019 Mar 27.

Reference Type BACKGROUND
PMID: 31147226 (View on PubMed)

Other Identifiers

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23-021140

Identifier Type: -

Identifier Source: org_study_id

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