Genetic DiseaseNCT06555965
STXBP1 and SYNGAP1 Related Disorders Natural History Study
An observational study of Genetic Disease and STXBP1 Encephalopathy With Epilepsy, run by Children's Hospital of Philadelphia at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Genetic Disease, STXBP1 Encephalopathy With Epilepsy, SYNGAP1-Related Intellectual Disability
- What is being tested?
- Non-interventional study
- How many people
- 600 participants
- Where
- 5 sitesUnited States
- Study dates
- 30 Aug 2023to 30 Dec 2028
- 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: Participating individuals must have a confirmed genetic diagnosis of STXBP1 or SYNGAP1 related disorders. Participants can be any age and present with any disease severity
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Victoria Chisari, BA, NS contact
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Children's Hospital Colorado
Aurora, Colorado, 80011
Megan Stringfellow, Megan.Stringfellow@childrenscolorado.org
Andrea Miele, PhD
- Recruiting
Texas Children's Hospital
Houston, Texas, 77030
Ekaterina Sanchez Romero, chao-lab@bcm.edu
Hsiao-Tuan Chao, MD, PhD
- Recruiting
Weill Cornell Medicine
New York, New York, 10065
Millie Stone, aks4017@med.cornell.edu
Zachary Grinspan, MD
- Recruiting
Stanford Medicine Children's Health
Palo Alto, California, 94304
Swetapadma Patnaik, sweta@stanford.edu
Juliet Knowles, MD
- Recruiting
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19403
Joeylynn Nolan, coynej@chop.edu
Ingo Helbig, MD
About this study
Official title: STXBP1 and SYNGAP1 Related Disorders (RD) Natural History Study
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.
Read the 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
- Conditions
- Genetic Disease, STXBP1 Encephalopathy With Epilepsy, SYNGAP1-Related Intellectual Disability
- Being tested
- Non-interventional study
- Keywords
- STXBP1, Natural History, Clinical Research, SYNGAP1
- Medical subject headings
- Genetic Diseases, Inborn, Epileptic Encephalopathy, Early Infantile, 4
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Non-interventional studyOther
There is no planned intervention in this study
| Study group | Role | What they receive |
|---|---|---|
| STXBP1 cohort | Not described Receives: Other: Non-interventional study | |
| SYNGAP1 cohort | Not described Receives: Other: Non-interventional study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in percentiles recorded on clinical assessments over time
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.
Measured: Every 6 months upto 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Aug 2024
- Study start30 Aug 2023
- Primary completion30 Aug 2028 (estimated)
- Study completion30 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Genetic DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- STXBP1 Foundation
- Responsible party
- Sponsor
- Investigators
- Ingo Helbig, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06555965
- Sponsor's protocol ID
- 23-021140
- Status last verified
- Oct 2025
- First submitted
- 13 Aug 2024
- Last updated
- 29 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 35190816Yang 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.
PubMed 35002943Wang 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.
PubMed 17012639Demarest 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.
PubMed 31147226
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- STXBP1 and SYNGAP1 Related Disorders (RD) Natural History Study
- ClinicalTrials.gov ID
- NCT06555965
- Acronym / sponsor ID
- 23-021140
- Conditions
- Genetic Disease, STXBP1 Encephalopathy With Epilepsy, SYNGAP1-Related Intellectual Disability
- Keywords
- STXBP1, Natural History, Clinical Research, SYNGAP1
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- STXBP1 Foundation
- Study start
- 30 Aug 2023 (actual)
- Primary completion
- 30 Aug 2028 (estimated)
- Study completion
- 30 Dec 2028 (estimated)
- First posted
- 15 Aug 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.
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| STXBP1 cohort | – | Other: Non-interventional study |
| SYNGAP1 cohort | – | Other: Non-interventional study |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Participating individuals must have a confirmed genetic diagnosis of STXBP1 or SYNGAP1 related disorders. Participants can be any age and present with any disease severity
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Non-interventional studyThere is no planned intervention in this study | Other | STXBP1 cohort, SYNGAP1 cohort |
Primary outcome
Changes in percentiles recorded on clinical assessments over time
Time frame: Every 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.
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 29 Oct 2025.
- Background: PubMed 35190816Xian 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.
- Background: PubMed 35002943Yang 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.
- Background: PubMed 17012639Wang 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.
- Background: PubMed 31147226Demarest 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.
- 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.
Victoria Chisari, BA, NS contact
Ingo Helbig, MD principal investigator
Children's Hospital of Philadelphia
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Genetic Disease and STXBP1 Encephalopathy With Epilepsy, run by Children's Hospital of Philadelphia at 5 sites in United States.
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 2 inclusion and 5 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 29 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. 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 Joeylynn Nolan, RRT NPS AE-C (2674411813, COYNEJ@chop.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in percentiles recorded on clinical assessments over time (time frame: Every 6 months upto 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06555965, which also lists 4 linked publications.
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 29 Oct 2025.