Clinical trial NCT05361070: Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy
Official title: Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy (NSR-GENE)
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Neonatal Seizure
Hypoxic-Ischemic Encephalopathy
Stroke
Intracranial Hemorrhage
Epilepsy
Gene Abnormality
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2022-05-04
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Outpatient, family members/caregivers, children/minors, participants unable to read, speak or understand English

Brief summary: The NSR-GENE study is a longitudinal cohort study of approximately 300 parent-child trios from the Neonatal Seizure Registry and participating site outpatient clinics that aims to evaluate whether and how genes alter the risk of post-neonatal epilepsy among children with acute provoked neonatal seizures. The researchers aim to develop prediction rules to stratify neonates into low, medium, and high risk for post-neonatal epilepsy based on clinical, electroencephalogram (EEG), magnetic resonance imaging (MRI), and genetic risk factors.

Detailed description: Neonatal seizures due to brain injury (acute provoked seizures) are associated with high risk of post-neonatal epilepsy. Although clinical risk factors can help predict which children are at highest risk for epilepsy, little is known about how genetic factors modify the risk for epilepsy after acute provoked neonatal seizures. The Neonatal Seizure Registry - GENetics of Epilepsy (NSR-GENE) study will test the central hypothesis that children who develop post-neonatal epilepsy are more likely to have pathogenic variants in epilepsy genes, and enrichment in single nucleotide polymorphisms within key inflammatory, neurotransmitter transport and homeostasis, and neurotrophic gene pathways as compared with children who do not develop unprovoked seizures before age five years, and that these can be added to traditional clinical risk factors to predict epilepsy after neonatal seizures.

Eligibility criteria: Inclusion Criteria:

* Children \< 44 weeks postmenstrual age at seizure onset
* Seizures due to an acute provoked cause (including, but not limited to HIE, ischemic stroke, or intracranial hemorrhage)
* Parent(s) who are English or Spanish literate (with interpreter)
* Birthdate between 3/1/2023 and 1/1/2011
* One biological parent willing to participate
* Enrolled in NSR-II
* Fulfilling all NSR-II eligibility criteria and evaluated at an NSR center for neonatal seizures or enrolled in NSR-RISE

Exclusion Criteria:

* Risk for adverse outcome independent of seizures and underlying brain injury (including but not limited to inborn errors of metabolism, fetal infection, brain malformation)
* Transient cause for seizures (e.g., hypoglycemia without brain injury, hyponatremia, hypocalcemia)
* Neonatal-onset epilepsy syndromes
* Deceased

Primary outcomes:
measure: Number of participants with post-neonatal epilepsy
timeFrame: 5 years of age
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Washington
country: United States
facility: Children's National Medical Center
state: District of Columbia
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
Study officials:
affiliation: University of California, San Francisco
name: Hannah C Glass, MDCM, MAS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shellhaas RA, Wusthoff CJ, Numis AL, Chu CJ, Massey SL, Abend NS, Soul JS, Chang T, Lemmon ME, Thomas C, McNamara NA, Guillet R, Franck LS, Sturza J, McCulloch CE, Glass HC. Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study. Epilepsia. 2021 Aug;62(8):1871-1882. doi: 10.1111/epi.16978. Epub 2021 Jul 2.
citation: Numis AL, da Gente G, Sherr EH, Glass HC. Whole-exome sequencing with targeted analysis and epilepsy after acute symptomatic neonatal seizures. Pediatr Res. 2022 Mar;91(4):896-902. doi: 10.1038/s41390-021-01509-3. Epub 2021 Apr 12.
citation: Glass HC, Grinspan ZM, Li Y, McNamara NA, Chang T, Chu CJ, Massey SL, Abend NS, Lemmon ME, Thomas C, McCulloch CE, Shellhaas RA; Neonatal Seizure Registry Study Group. Risk for infantile spasms after acute symptomatic neonatal seizures. Epilepsia. 2020 Dec;61(12):2774-2784. doi: 10.1111/epi.16749. Epub 2020 Nov 13.
citation: Glass HC, Grinspan ZM, Shellhaas RA. Outcomes after acute symptomatic seizures in neonates. Semin Fetal Neonatal Med. 2018 Jun;23(3):218-222. doi: 10.1016/j.siny.2018.02.001. Epub 2018 Feb 6.
citation: Bennett ER, Reuter-Rice K, Laskowitz DT. Genetic Influences in Traumatic Brain Injury. In: Laskowitz D, Grant G, editors. Translational Research in Traumatic Brain Injury. Boca Raton (FL): CRC Press/Taylor and Francis Group; 2016. Chapter 9. Available from http://www.ncbi.nlm.nih.gov/books/NBK326717/
citation: Wong VS, Langley B. Epigenetic changes following traumatic brain injury and their implications for outcome, recovery and therapy. Neurosci Lett. 2016 Jun 20;625:26-33. doi: 10.1016/j.neulet.2016.04.009. Epub 2016 May 4.
citation: Christensen J, Pedersen MG, Pedersen CB, Sidenius P, Olsen J, Vestergaard M. Long-term risk of epilepsy after traumatic brain injury in children and young adults: a population-based cohort study. Lancet. 2009 Mar 28;373(9669):1105-10. doi: 10.1016/S0140-6736(09)60214-2. Epub 2009 Feb 21.
citation: Eriksson H, Wirdefeldt K, Asberg S, Zelano J. Family history increases the risk of late seizures after stroke. Neurology. 2019 Nov 19;93(21):e1964-e1970. doi: 10.1212/WNL.0000000000008522. Epub 2019 Oct 23.