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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Epilepsy; Hypoxic-Ischemic Encephalopathy; Neonatal Seizure; Intracranial Hemorrhage; Gene Abnormality

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.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Hannah C Glass, MDCM, MAS; Phone Number: 415-476-3785; Email: hannah.glass@ucsf.edu
• Study Contact Backup: Name: Yasmeen A Rezaishad, BS; Phone Number: 415-476-3785; Email: yasmeen.rezaishad@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California, San Francisco
      • Contact: Yasmeen A Rezaishad, BS; Phone Number: 415-476-3785; Email: yasmeen.rezaishad@ucsf.edu
      • Principal Investigator: Hannah C Glass, MDCM, MAS
      • Principal Investigator: Elliott Sherr, MD, PhD
      • Sub-Investigator: Adam Numis, MD
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Recruiting
      • Children's National Medical Center
      • Principal Investigator: Tayyba Anwar, MD
      • Contact: Courtney Reed; Phone Number: 202-476-3807; Email: clowe@childrensnational.org
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Contact: Jessica Landers, MS; Phone Number: 617-355-0578; Email: jessica.landers@childrens.harvard.edu
      • Principal Investigator: Janet Soul, MD
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
      • Principal Investigator: Catherine Chu, MD
      • Contact: Skyler Goodman; Phone Number: 617-249-4939; Email: sgoodman8@mgh.harvard.edu
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Stephanie Rau, BS, CCRP; Phone Number: 734-232-8474; Email: shatchew@med.umich.edu
      • Principal Investigator: Renee A Shellhaas, MD, MS
      • Contact: Brittany Nordhaus
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Recruiting
      • Duke University
      • Contact: Jessicka Hamilton, MA; Email: jessicka.hamilton@duke.edu
      • Principal Investigator: Monica E Lemmon, MD
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Recruiting
      • Cincinnati Children's Hospital Medical Center
      • Contact: Madeleine Robben; Phone Number: 513-636-5511; Email: madeleine.robben@cchmc.org
      • Principal Investigator: Cameron Thomas, MD, MS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Children's Hospital of Philadelphia
      • Contact: Darshana Parikh, BA; Email: parikhd@email.chop.edu
      • Principal Investigator: Nicholas Abend, MD, MSCE

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Outpatient, family members/caregivers, children/minors, participants unable to read, speak or understand English

Description

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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute of Neurological Disorders and Stroke (NINDS)
• Investigators: Principal Investigator: Hannah C Glass, MDCM, MAS, University of California, San Francisco

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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/
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 9, 2022
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: April 29, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 7, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain; Epilepsy; Brain Ischemia; Hemorrhage; Seizures; Brain Diseases; Intracranial Hemorrhages; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: 21-35563; R01NS124051 (U.S. NIH Grant/Contract); R01NS124051-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: In accordance with study sponsor
• IPD Sharing Time Frame: In accordance with study sponsor
• IPD Sharing Access Criteria: In accordance with study sponsor

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No