Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy

Stroke Clinical Trial

— NSR-GENE  

Official title:

Neonatal Seizure Registry, GEnetics of Post-Neonatal Epilepsy (NSR-GENE)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05361070
• Other study ID #: 21-35563
• Secondary ID: R01NS124051R01NS
• Status: Recruiting
• Start date: August 9, 2022
• Est. completion date: February 28, 2027

Study information

• Verified date: March 2024
• Source: University of California, San Francisco
• Contact: Hannah C Glass, MDCM, MAS
• Phone: 415-476-3785
• Email: hannah.glass[@]ucsf.edu
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: February 28, 2027
• Est. primary completion date: February 28, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Epilepsy
• Gene Abnormality
• Hemorrhage
• Hypoxia-Ischemia, Brain
• Hypoxic-Ischemic Encephalopathy
• Intracranial Hemorrhage
• Intracranial Hemorrhages
• Neonatal Seizure
• Seizures
• Stroke

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Duke University	Durham	North Carolina
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	University of California, San Francisco	San Francisco	California
United States	Children's National Medical Center	Washington	District of Columbia

Sponsors (2)

Lead Sponsor	Collaborator
University of California, San Francisco	National Institute of Neurological Disorders and Stroke (NINDS)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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/ — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with post-neonatal epilepsy	The presence or absence of a post-neonatal epilepsy diagnosis at age 5 in children with a prior history of acute symptomatic neonatal seizures will be determined by telephone interview with the parent and corroborated by medical record review	5 years of age