Clinical trial NCT03822741: Etiology and Treatment of Neonatal Seizure
Official title: Gene Profiling and Individualized Treatment of Neonatal Seizure in China
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Seizures
Seizure Disorder
Seizure Newborn
Seizure Generalized
Keywords: seizure
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
First posted: 2019-01-30
Enrollment: 2000
Sex: ALL
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: CASE_ONLY
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The subjects were treated in the Department of Neonatology of Children Hospital of Fudan University. All samples in this study were collected with appropriate informed consent and approval of the ethics committee of Children's Hospital, Fudan University. The methods used in this study were carried out in accordance with the approved guidelines.

Brief summary: Genetic diagnosis for neonates suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies. Investigator performed exome sequencing (ES) or targeted sequencing on neonates with seizure onset within the first month of life. Investigator subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1-12 months), to compare the clinical and genetic features and treatment strategies.

Detailed description: Seizure is one of the most common neurological conditions in neonates, and has substantial impact on patients'quality of life and social integration. Epileptic encephalopathy is characterized by refractory seizures, cognitive dysfunction, and poor prognosis. Despite the recent progress in technology, molecular diagnosis of neonates suffering from possible epileptic seizures can be challenging, due to genetic and phenotypic heterogeneities. A large number of specific pathogenic variations have been related to various forms of epilepsies. Next-generation sequencing (NGS) has significantly improved the molecular diagnosis for rare diseases. NGS focusing on genes known to be associated with human diseases is a practical approach as a first-tier assessment for patients with heterogeneous genetic background. In addition, currently medical therapy for seizure is not based on the etiology, but the clinical manifestations, and the main purpose is not to rescue the underlying diseases process, but just to reduce the likelihood of seizures occurrence. In this study, Investigator performed NGS on neonates with seizure onset before 1 year of age, to detect and quantify genetic variants, and assess existing therapeutic effects. Our findings will have important implications for the development of precision medicine strategies.

Eligibility criteria: Inclusion Criteria:

* severe seizures in neonates or generalized epilepsy or intractable epilepsy in infancy with generalized tonic-clonic seizures,
* seizures onset before 1 year of age,
* epileptic syndromes/epileptic-encephalopathies with unknown etiology.

Exclusion Criteria:

* Patients were excluded if they had traumas, central nervous system infections, hypoxic-ischemic encephalopathy, vascular events, systemic infections, and diagnosed metabolic disorders, and pathogenic copy-number variants were identified using array-based comparative genomic hybridization (CGH).

Primary outcomes:
measure: Mutation rate of common seizure genes
timeFrame: From the oneset of seizure to the genetic sequencing finish, the process may last up to 3 months.
measure: Rate of seizure free
timeFrame: From the onset of seizure to 6 months after the onset of seizure
Secondary outcomes:
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Wenhao Zhou, Doctor
role: STUDY_CHAIR
References:
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