Evaluating the Role of Inflammation in Neonatal Epileptogenesis

NCT ID: NCT04259125

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 72 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-12-15
• Study Completion Date: 2025-12-01

Brief Summary

The purpose of this study evaluate the relationship between inflammation and epilepsy in neonates with seizures after birth.

Detailed Description

Seizures are a common symptom of neurologic dysfunction in the neonatal period, affecting more than 16,000 newborns in the United States per year. Over 25% of neonates with acute symptomatic seizures develop post- neonatal epilepsy (PNE), which is often resistant to medical therapies. There is a critical need to identify those patients most at risk for PNE and understand the mechanisms by which early seizures increase the propensity for recurrent seizures, in hopes of identifying novel therapeutic targets in this population. There is increasing evidence for the role of neuro-inflammation in the development of epilepsy. Levels of cytokines and micro-RNA (miRNA) may serve as markers of disease severity and have been implicated in epileptogenesis in animal models. The purpose of this study is to evaluate plasma cytokine and miRNA levels after neonatal-onset acute symptomatic seizures and determine their association with acute seizure severity and PNE.

Conditions

Neonatal Seizure; Epilepsy; Seizures; Inflammatory Response

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Acute symptomatic seizures

This is a cohort of 72 participants who will be enrolled into this study from the neonatal intensive care unit (NICU) after being diagnosed with seizures. They will be asked to contribute a blood specimen obtained ideally 48-96 hours (though blood collection allowed 24-120 hours) after seizures are diagnosed, to participate in an optional blood draw at 2-4 months of age, and to complete surveys at 12 \& 24 months of age.

Blood draw

Intervention Type: DIAGNOSTIC_TEST

Evaluation of plasma inflammatory markers including cytokines and micro-RNA.

Survey

Intervention Type: OTHER

Regarding epilepsy and development.

Control

This is a cohort of 15 participants who will be enrolled into this study from the neonatal intensive care unit (NICU) after having an EEG for possible seizures, but found to have a normal EEG. They will be asked to contribute a blood specimen obtained ideally 48-96 hours (though blood collection allowed 24-120 hours) after birth.

Blood draw

Intervention Type: DIAGNOSTIC_TEST

Evaluation of plasma inflammatory markers including cytokines and micro-RNA.

Interventions

Blood draw

Evaluation of plasma inflammatory markers including cytokines and micro-RNA.

Intervention Type: DIAGNOSTIC_TEST

Survey

Regarding epilepsy and development.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Neonates <44 weeks corrected age at seizure onset
• Seizures due to acute brain injury
• Parent(s) who are English or Spanish literate (with assistance of interpreter)

• Neonates that are born > 37 weeks and <44 weeks postmenstrual age at enrollment
• Consultation by the pediatric neurology inpatient service due neonatal paroxysmal events, with normal neurologic examination and ultimate diagnosis of non-epileptic spells on continuous video-EEG (ordered for clinical purposes, not for research) OR consultation for hypoxic ischemic encephalopathy in neonates undergoing therapeutic hypothermia, with early exit from therapy owing to normal neurologic examination, normal continuous video-EEG and uncertain diagnosis of encephalopathy.
• Neonates requiring neurologic consultation for mild hypoxic-ischemic encephalopathy (HIE) undergoing therapeutic hypothermia, with normal examination, cEEG, and neuroimaging upon rewarming.

Exclusion Criteria

• Neonates at risk for adverse outcome independent of seizures and underlying brain injury
• Neonates with mild, temporary causes for seizures
• Newborns with neonatal-onset epilepsy syndromes
• Neonates who do not survive the initial hospital admission
• Neonates will not be excluded based on race, ethnicity, gender or gestational age

For participants in the control group:

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 4 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Michigan

OTHER

Sponsor Role: collaborator

Boston Children's Hospital

OTHER

Sponsor Role: collaborator

UCSF Benioff Children's Hospital Oakland

OTHER

Sponsor Role: collaborator

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Adam L Numis, MD

Role: PRINCIPAL_INVESTIGATOR

University of California, San Francisco

Locations

UCSF Benioff Children's Hospital Oakland

Oakland, California, United States

University of California, San Francisco

San Francisco, California, United States

Boston Children's Hospital

Boston, Massachusetts, United States

University of Michigan, Mott Children's Hospital

Ann Arbor, Michigan, United States

Countries

United States

References

Numis AL, Foster-Barber A, Deng X, Rogers EE, Barkovich AJ, Ferriero DM, Glass HC. Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy. Pediatr Res. 2019 Nov;86(5):616-621. doi: 10.1038/s41390-019-0473-x. Epub 2019 Jun 24.

Reference Type: BACKGROUND

PMID: 31234194 (View on PubMed)

Other Identifiers

K23NS105918

Identifier Type: NIH

Identifier Source: secondary_id

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K23NS105918

Identifier Type: NIH

Identifier Source: org_study_id

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