Evaluating the Role of Inflammation in Neonatal Epileptogenesis

Epilepsy Clinical Trial

— NSR-RISE  

Official title:

Neonatal Seizure Registry: The Role of Inflammation After Neonatal Seizures and Later Development of Epilepsy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04259125
• Other study ID #: K23NS105918
• Secondary ID: K23NS105918
• Status: Active, not recruiting
• Start date: December 15, 2018
• Est. completion date: November 30, 2024

Study information

• Verified date: August 2023
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 87
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Gender: All
• Age group: 1 Day to 4 Days

Eligibility

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.

Related Conditions & MeSH terms

• Epilepsy
• Inflammation
• Inflammatory Response
• Neonatal Seizure
• Seizures

Intervention

Diagnostic Test:
• Blood draw
Evaluation of plasma inflammatory markers including cytokines and micro-RNA.

Other:
• Survey
Regarding epilepsy and development.

Locations

Country	Name	City	State
United States	University of Michigan, Mott Children's Hospital	Ann Arbor	Michigan
United States	Boston Children's Hospital	Boston	Massachusetts
United States	UCSF Benioff Children's Hospital Oakland	Oakland	California
United States	University of California, San Francisco	San Francisco	California

Sponsors (5)

Lead Sponsor	Collaborator
University of California, San Francisco	Boston Children's Hospital, National Institute of Neurological Disorders and Stroke (NINDS), UCSF Benioff Children's Hospital Oakland, University of Michigan

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Seizure burden	Investigators will evaluate the seizure burden from the initial diagnostic electroencephalogram (EEG) after birth by determining the average number of seizures per hour.	At study entry
Primary	Percentage of participants diagnosed with epilepsy	The investigators will determine the proportion of participants who develop clinical and or electrographic seizures.	24 months of age
Secondary	Percentage of participants diagnosed with epilepsy	The investigators will determine the proportion of participants who develop clinical and or electrographic seizures.	12 months of age
Secondary	Epilepsy Severity	The investigators will administer an investigator-developed questionnaire designed to define the frequency of seizures (monthly, weekly, daily, or greater than daily).	12 months of age
Secondary	Epilepsy Severity	The investigators will administer an investigator-developed questionnaire designed to define the frequency of seizures (monthly, weekly, daily, or greater than daily).	24 months of age
Secondary	Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)	The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be assessed at 12 months of age. The score ranges from 50 to 200 with higher scores associated with normal development.	Assessment takes up to 15 minutes and will be conducted at 12 months of age
Secondary	Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS)	The Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) will be assessed at 24 months of age. The score ranges from 50 to 200 with higher scores associated with normal development.	Assessment takes up to 15 minutes and will be conducted at 24 months of age