Molecular Genetic Mechanisms of Infantile Epilepsies and the Impact of Genetic Diagnosis

Not Applicable

Recruiting

• Conditions: Neonatal Epilepsy; Infantile Epilepsy

• Registration Number: NCT06701084
• Lead Sponsor: Boston Children's Hospital

Brief Summary

The goal of this study is to discover new genetic causes of infantile epilepsies and evaluate the impact of these discoveries on infants with epilepsy and their families.

Detailed Description

Infantile epilepsies are common, affecting 1 in 1000 infants, and are associated with significant morbidity, mortality, healthcare costs, and caregiver burden. Although most infantile epilepsies are believed to have genetic causes, most infants with epilepsy remain genetically "unsolved" and the full genetic landscape of infantile epilepsies is unknown, which limits our ability to develop precision therapies and ultimately improve outcomes for this vulnerable population. This study aims to discover new genetic causes of infantile epilepsies and evaluate the impact of these discoveries on infants with epilepsy and their families, contributing to knowledge that will inform our scientific understanding of normal and abnormal brain development and guide clinical care and implementation of precision medicine for infants with epilepsy.

Study Timeline

• Study Start: 2021-09-02
• Status Verified: 2024-11
• Study First Submitted: 2024-11-19
• Study First Submitted QC: 2024-11-21
• Last Update Submitted: 2024-11-21
• Study First Posted: 2024-11-22
• Last Update Posted: 2024-11-22
• Primary Completion: 2029-11
• Study Completion: 2029-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 600

Inclusion Criteria

• Seizure onset at less than 12 months of age
• Enrollment within 6 weeks of seizure-related presentation
• Patient at Boston Children's Hospital

Exclusion Criteria

• Simple febrile seizures
• Acute provoked seizures (e.g., due to sepsis, hemorrhage, electrolyte abnormality, cerebral infarction, hypoxic ischemic encephalopathy, non-accidental injury)
• Genetic or acquired cause of epilepsy already identified, including brain magnetic resonance imaging findings consistent with a specific genetic etiology (e.g., tuberous sclerosis complex)
• Deceased prior to enrollment

Parent Criteria Inclusion Criteria - Parent of eligible infant (see above)

Exclusion Criteria

• Not the legal guardian of the eligible infant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
Diagnostic Yield	Collected after return of genetic results approximately 2 weeks after infant is enrolled	The diagnostic yield of genomic sequencing will be calculated as the percentage of enrolled infants with epilepsy who receive a genetic diagnosis.
Short-term clinical utility of genetic testing	Collected after return of genetic results approximately 2 weeks after infant is enrolled	The short-term clinical utility of genetic testing will be evaluated using the validated C-GUIDE measure. The C-GUIDE total score will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.
Parent-perceived (personal) utility of genetic testing	Collected when infant is 2.5 years old	The parent-perceived utility of genetic testing will be evaluated using the validated GENE-U measure. The GENE-U total score will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.

Secondary Outcome Measures

Name	Time	Method
Developmental progress	Collected when infant is 2.5 years old	Developmental progress will be evaluated using the Bayley Scales of Infant and Toddler Development Fourth Edition. The cognitive, language, and motor subscale scores will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.
Seizure frequency	Collected at return of genetic results approximately 2 weeks after infant is enrolled and when infant is 2.5 years old	The seizure frequency will be evaluated using the seizure frequency outcome measure developed by the American Academy of Neurology and dichotomized as decrease vs no decrease between the two timepoints. The percentage of infants with this outcome will be compared between infants with epilepsy who did vs did not receive a genetic diagnosis.
Parental experiences with genetic testing	Collected when infant is 2.5 years old	This outcome will be evaluated using a qualitative approach. Semi-structured interviews will be performed with a subset of parents using purposive sampling and will be analyzed using a grounded theory iterative approach.

Trial Locations

Locations (1)

Boston Children's Hospital; 🇺🇸 Boston, Massachusetts, United States