# HEAL - EEG - Neurophysiologic measures of Epo treatment for hypoxic-ischemic encephalopathy (HIE)

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $346,712

## Abstract

Project Summary
The objective of this application is to leverage the infrastructure of the NINDS-funded multicenter, randomized,
placebo-controlled Phase III HEAL (High-Dose Erythropoietin for Asphyxia and Encephalopathy) clinical trial of
erythropoietin (Epo) vs. placebo for neuroprotection in neonates with moderate/severe hypoxic-ischemic
encephalopathy (HIE) who also receive therapeutic hypothermia to determine the effect of Epo on important
continuous, video electroencephalogram (cEEG) measures. The proposed “HEAL-EEG” sub-study of the
parent HEAL trial will test the central hypotheses that neonates who receive Epo will have a lower burden of
neonatal seizures, and that cEEG background abnormalities and seizure burden will be associated with
developmental disability at 2 years in both the placebo and Epo groups. We will test our hypotheses by
pursuing two specific aims: 1) To determine whether neonates who receive Epo have a lower seizure burden
than those who receive placebo and to assess whether lower seizure burden is associated with lower risk of
adverse neurodevelopmental outcome and epilepsy, 2a) To determine whether neonates who receive Epo
have altered cEEG background and to assess the ability of cEEG to predict adverse developmental outcome in
neonates who receive Epo as compared to those who receive hypothermia alone, and 2b) To determine
whether there is incremental added accuracy in predicting neurodevelopmental outcome at 2 years when
adding cEEG seizure burden and background to clinical examination and MRI injury score. cEEG from 150
subjects enrolled in HEAL will be analyzed by two neurophysiologists with expertise in neonatal EEG for
seizures and background patterns to compare seizure burden in Epo and placebo groups, as well as to
examine the relationship between cEEG background pattern at six specified time points and
neurodevelopmental outcome using Bayley Scales of Infant and Toddler Development, 3rd edition at 2 years.
Upon successful completion of the proposed research, we expect our contribution to be a detailed
understanding of how Epo affects seizure burden in neonates with HIE, as well as the predictive value of EEG
in neonates undergoing hypothermia with and without Epo. The approach is innovative because it leverages
the prospective randomized, controlled HEAL trial to evaluate critical cEEG measures in a way that cannot be
accomplished in longitudinal cohort studies. HEAL-EEG will be the largest study to carefully evaluate detailed
cEEG measures in a multicenter setting of a novel neuroprotective agent. The research is significant because
it will add to our understanding of Epo’s mechanism of action, as well as inform clinicians in the rational
utilization of cEEG in neonates with HIE by defining the risk and timing of seizures, as well as the prognostic
utility of cEEG at various time points during and after hypothermia. Using tools like cEEG to predict
neurodevelopmental outcome for neonates with HIE at the earl...

## Key facts

- **NIH application ID:** 10200910
- **Project number:** 5R01NS104322-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Hannah Cranley Glass
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $346,712
- **Award type:** 5
- **Project period:** 2018-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10200910

## Citation

> US National Institutes of Health, RePORTER application 10200910, HEAL - EEG - Neurophysiologic measures of Epo treatment for hypoxic-ischemic encephalopathy (HIE) (5R01NS104322-04). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10200910. Licensed CC0.

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