Clinical trial NCT04259125: Evaluating the Role of Inflammation in Neonatal Epileptogenesis
Official title: Neonatal Seizure Registry: The Role of Inflammation After Neonatal Seizures and Later Development of Epilepsy
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Neonatal Seizure
Epilepsy
Seizures
Inflammatory Response
Keywords: Neonatal seizure
Inflammation
Cytokine
Micro-RNA
Epilepsy
EEG
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: University of Michigan
name: Boston Children's Hospital
name: UCSF Benioff Children's Hospital Oakland
name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2020-02-06
Enrollment: 87
Sex: ALL
Minimum age (years): 1
Maximum age (years): 4
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Newborns who are admitted at one of the participating children's hospitals

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.

Eligibility criteria: For participants in the acute symptomatic seizure group:

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)

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:

Inclusion Criteria:

* 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.

Primary outcomes:
measure: Seizure burden
timeFrame: At study entry
measure: Percentage of participants diagnosed with epilepsy
timeFrame: 24 months of age
Secondary outcomes:
measure: Percentage of participants diagnosed with epilepsy
timeFrame: 12 months of age
measure: Epilepsy Severity
timeFrame: 12 months of age
measure: Epilepsy Severity
timeFrame: 24 months of age
measure: Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)
timeFrame: Assessment takes up to 15 minutes and will be conducted at 12 months of age
measure: Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)
timeFrame: Assessment takes up to 15 minutes and will be conducted at 24 months of age
Other outcomes:
Locations:
city: Oakland
country: United States
facility: UCSF Benioff Children's Hospital Oakland
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan, Mott Children's Hospital
state: Michigan
Study officials:
affiliation: University of California, San Francisco
name: Adam L Numis, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.