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

HEAL - 脑电图 - Epo 治疗缺氧缺血性脑病 (HIE) 的神经生理学措施

• 批准号: 10200910
• 负责人: Hannah Cranley Glass
• 金额: $ 34.67万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10200910
• 关键词: Acute; Adult; Affect; Animal Model; Asphyxia; Brain; Brain Injuries; Caring; Cerebral Palsy; Cerebrum; Cessation of life; Child; Clinical; Clinical Data; Clinical Trials; Cognitive; Cohort Studies; Communication; Convulsants; Data; Data Coordinating Center; Development; Developmental Disabilities; Dose; Electroencephalogram; Electroencephalography; Encephalopathies; Enrollment; Epilepsy; Erythropoietin; Evaluation; Family; Functional disorder; Funding; Gold; Individual; Infant; Infrastructure; Injury; Kidney Diseases; Knowledge; Label; Length; Longitudinal cohort study; Magnetic Resonance Imaging; Measures; Mission; Modeling; Monitor; Multicenter Trials; National Institute of Neurological Disorders and Stroke; Neonatal; Neuroprotective Agents; Outcome; Parents; Pattern; Phase; Placebos; Predictive Value; Provider; Public Health; Randomized; Research; Rewarming; Risk; Seizures; Severities; Site; Specific qualifier value; Testing; Therapeutic; Time; Toddler; base; clinical decision-making; clinical examination; clinically relevant; disability; improved; innovation; insight; natural hypothermia; neonatal hypoxic-ischemic brain injury; neonatal seizure; neonate; nervous system disorder; neurodevelopment; neurological recovery; neurophysiology; neuroprotection; novel; placebo group; predictive modeling; prognostic value; prospective; randomized trial; secondary analysis; tool; treatment group

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 earliest possible time point is critical for clinical decision-making and parent communication.

项目概要 该应用程序的目标是利用 NINDS 资助的多中心、随机、 安慰剂对照 III 期 HEAL（高剂量促红细胞生成素治疗窒息和脑病）临床试验 促红细胞生成素 (Epo) 与安慰剂对中度/重度缺氧缺血新生儿的神经保护作用 脑病 (HIE) 患者也接受低温治疗以确定 Epo 对重要疾病的影响 连续视频脑电图（cEEG）测量 拟议的“HEAL-EEG”子研究。 家长 HEAL 试验将测试以下中心假设：接受 EPO 的新生儿将有较低的负担 新生儿癫痫发作，并且 cEEG 背景异常和癫痫发作负担与 安慰剂组和 EPO 组在 2 岁时出现发育障碍 我们将通过以下方式检验我们的假设。 追求两个具体目标：1) 确定接受 EPO 的新生儿癫痫发作负担是否较低 与接受安慰剂的患者相比，并评估较低的癫痫发作负担是否与较低的风险相关 不良神经发育结果和癫痫，2a) 确定接受 Epo 的新生儿是否 改变了 cEEG 背景并评估 cEEG 预测不良发育结果的能力 接受 EPO 的新生儿与仅接受低温治疗的新生儿进行比较，以及 2b) 确定 预测 2 岁时的神经发育结果是否会增加准确性 将 cEEG 癫痫发作负担和背景添加到临床检查和 MRI 损伤评分中（150）。 参加 HEAL 的受试者将由两名具有新生儿脑电图专业知识的神经生理学家进行分析 癫痫发作和背景模式，以比较 EPO 组和安慰剂组的癫痫发作负担，以及 检查六个指定时间点的 cEEG 背景模式之间的关系 使用婴儿和幼儿发育贝利量表（第 3 版）2 岁时的神经发育结果。 成功完成拟议的研究后，我们希望我们的贡献是详细的 了解 Epo 如何影响 HIE 新生儿的癫痫发作负担，以及 EEG 的预测价值 该方法是创新的，因为它利用了 EPO。 前瞻性随机对照 HEAL 试验，以一种无法预测的方式评估关键的 cEEG 测量 HEAL-EEG 是在纵向队列研究中完成的，将是仔细评估详细信息的最大研究。 这项研究在多中心环境中测量新型神经保护剂具有重要意义。 它将增加我们对EPO作用机制的理解，并告知居民合理的使用方法。 通过定义癫痫发作的风险和时间以及预后，将 cEEG 用于患有 HIE 的新生儿 cEEG 在低温期间和之后不同时间点的效用 使用 cEEG 等工具进行预测。 尽早获得 HIE 新生儿的神经发育结果对于临床至关重要 决策和家长沟通。