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: 9790993
• 负责人: Hannah Cranley Glass
• 金额: $ 39.2万
• 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 2022-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9790993
• 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; clinically relevant; disability; improved; innovation; insight; natural hypothermia; neonatal hypoxic-ischemic brain injury; 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.

项目摘要 该应用的目的是利用Ninds资助的多中心的基础架构，随机， 安慰剂对照的III期治疗（用于窒息和脑病的高剂量红细胞生成素）的临床试验 红细胞生成素（EPO）与安慰剂，用于中度/重度缺血性的新生儿神经保护作用 脑病（HIE）也接受治疗性体温过低，以确定EPO对重要的影响 连续的，视频脑电图（CEEG）的措施。拟议的“治疗”子研究 父母治疗试验将检验中心假设，即接受EPO的新生儿将其燃烧较低 新生儿癫痫发作，CEEG背景异常和癫痫发作将与 安慰剂和EPO组的发展残疾在2年中。我们将通过 追求两个具体的目标：1）确定接受EPO的新生儿是否有较低的癫痫发作 比那些接受安慰剂并评估下癫痫发作的人是否与较低的风险有关 不良神经发育结果和癫痫病，2a），以确定接受EPO的新生儿是否是否接受 改变了CEEG背景并评估CEEG预测不良发展结果的能力 与单独接受体温过低的人相比，接受EPO的新生儿和2b）确定 在预测2年的神经发育结果时是否有增量的准确性 在临床检查和MRI损伤评分中添加CEEG癫痫发作和背景。 CEEG从150起 在新生儿脑电图中具有专业知识的两位神经生理学家将分析入学的受试者 比较EPO和安慰剂组的癫痫发作和背景模式，以及 检查CEEG背景模式在六个指定时间点和 使用婴儿和幼儿发展的Bayley量表的神经发育结果，第3版2年。 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新生儿的癫痫发作以及脑电图的预测价值 在接受和没有EPO的下温度的新生儿中。这种方法是创新的，因为它利用了 前瞻性随机，受控的治疗试验，以评估关键的CEEG措施以不可能是 在纵向队列研究中完成。 Heal-EEG将是仔细评估详细评估的最大研究 CEEG在新型神经保护剂的多中心设置中进行测量。这项研究很重要，因为 这将增加我们对EPO的行动机制的理解，并向临床医生提供理性的信息 通过定义癫痫发作的风险和时机以及预后 CEEG在体温过低期间和之后的各个时间点的效用。使用CEEG等工具预测 在最早可能的时间点的新生儿的神经发育结果对于临床至关重要 决策和父母沟通。