CARE4Kids: Blood Biomarker Core

CARE4Kids：血液生物标志物核心

• 批准号: 10203602
• 负责人: JEFFREY John BAZARIAN
• 金额: $ 48.86万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-08 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10203602
• 关键词: Acute; Adolescence; Adolescent; Affect; Age; Algorithms; American; Biochemical; Biological; Biological Markers; Blood; Blood specimen; Brain; Brain Concussion; Caring; Categories; Clinical; Clinical Management; Clinical Treatment; Clinical Trials; Collection; Common Data Element; Data; Development; Dizziness; Early identification; Ensure; Evaluation; Future; Goals; Headache; Human Resources; Image; Inflammation; Inflammatory; Injury; Intervention; Lipids; Measurement; Measures; Membrane; Memory; Methods; Mission; Molecular; Monitor; National Institute of Neurological Disorders and Stroke; Neurons; Neuropeptides; Neurotransmitters; Oxidative Stress; Pathway interactions; Peptides; Phenotype; Physiological; Physiological Processes; Populations at Risk; Post-Concussion Syndrome; Procedures; Process; Protein Analysis; Proteins; Protocols documentation; Psychophysiology; Publishing; Quality Control; Radiology Specialty; Recovery; Reporting; Reproducibility; Research Personnel; Research Project Grants; Resources; Risk; Schools; Site; Standardization; Symptoms; Technical Expertise; Techniques; Time; Training; Work; Youth; age group; axon injury; base; biobank; blood-based biomarker; cognitive function; critical period; cytokine; data quality; design; disability; emotional functioning; endophenotype; executive function; experience; falls; genetic analysis; high risk; imaging biomarker; improved; medical specialties; neurodevelopment; neuroimaging; neurotransmission; novel; peripheral blood; prediction algorithm; prevent; preventive intervention; prospective; repository; risk stratification; sample collection; social; specific biomarkers; success; targeted treatment; trait; white matter change; young adult

PROJECT SUMMARY/ABSTRACT – Blood Biomarker Core Concussions affect nearly 3 million Americans annually (up to 1.9 million under the age of 18), with up to 15- 30% not recovered 3 months after injury. The risk of concussion is 5 times higher among early and middle adolescents (EMA) than any other age group, highlighting the need to focus on this at-risk population. Because early and middle adolescence is a critical period for neurodevelopment processes required for optimal cognitive, emotional, and executive functioning, EMAs may be at increased risk for the burden of long-term symptoms and deficits after concussion. Clinical trials to develop symptom-targeted therapies to facilitate recovery and to prevent long-term disability among EMAs are urgently needed. To optimize future trials, an accurate, prospective identification of those at the greatest risk for persistent post-concussive symptoms (PPCS; post-concussive symptoms lasting >3 months) and who would benefit from preventive interventions is essential. The overall goal of CARE4Kids is to identify and validate the most sensitive, specific, and scalable biomarkers to stratify PPCS risk and identify underlying endophenotypes. These biomarkers fall into 3 broad categories: blood-based, neuroimaging, and autonomic. The Blood Biomarker Core (BBC) will provide the necessary resources and technical expertise to collect, measure and analyze a panel of blood-based biomarkers (BBMs) reflecting key physiologic post-concussion processes, including axonal injury, inflammation, membrane turnover, oxidative stress and altered neurotransmission. Specific Aim 1: The BBC will make technically robust measurements of prospective blood biomarkers including neuronal/glial proteins, lipids, inflammatory cytokines, and neuropeptide neurotransmitters using well-validated analytic approaches. Data quality will be assured by compliance with standard operating procedures and continuous evaluation of technical reproducibility. Data will be reported to the Data Coordinating Core (DCC). Specific Aim 2: The BBC will work closely with BioSEND and the DCC to ensure that blood collection, storage, and measurement protocols are standardized across all study sites, including 1) the use of National Institute of Neurological Disorders and Stroke Common Data Elements related to biomarker collection, 2) ongoing training of study personnel, and 3) ongoing quality control. Specific Aim 3: The BBC will interact with the Administrative Core and integrate with the Imaging Biomarker Core and Autonomic Biomarker Core to determine how BBMs may enhance characterization of PPCS endophenotypes and improve accuracy of PPCS prediction by 1) characterizing BBM-specific measures in relation to PPCS endophenotypes, and 2) analyzing BBM data. At the conclusion of this project, we will not only develop a PPCS risk stratification algorithm that is practical, scalable, and accurate, we will identify the unique contribution of BBMs to PPCS in EMAs. Our results have potential to identify potentially modifiable inflammatory pathways and to elucidate the biologic mechanism underlying symptomatic recovery in this age group.

项目摘要/摘要 - 血液生物标志物核心 脑震荡每年影响近300万美国人（18岁以下的190万），最多15-- 受伤3个月后30％未恢复。早期和中间的咨询风险是5倍 青少年（EMA）都比任何其他年龄段，强调需要专注于这种高危人群。因为 早期和中部青少年是最佳认知所需的神经发育过程的关键时期 EMA的情绪和执行功能，可能会增加长期症状的伯宁风险 咨询后的缺陷。临床试验以开发针对症状的疗法，以促进恢复和 迫切需要防止EMA的长期残疾。为了优化未来的试验，一个准确，准的 识别持续脑后症状的风险最大的人（PPC；脑后 持续> 3个月的症状）至关重要。总体目标 Care4Kids的识别和验证最敏感，特定和可扩展的生物标志物以对PPC进行分层 风险并识别潜在的内表型。这些生物标志物分为3个广泛类别：基于血液， 神经影像学和自主神经。血液生物标志物核心（BBC）将提供必要的资源和 收集，测量和分析一组血液基标记物（BBM）的技术专长，反映密钥 生理后脑震荡过程，包括轴突损伤，感染，膜更新，氧化 压力和神经传递改变。特定目的1：英国广播公司将在技术上进行强大的测量 前瞻性血液标志物，包括神经元/神经胶质蛋白，脂质，炎症细胞因子和神经肽 神经递质使用验证良好的分析方法。数据质量将通过遵守 标准操作程序和技术复制的持续评估。数据将报告给 数据协调核心（DCC）。特定目标2：英国广播公司将与BioSend和DCC紧密合作 确保在所有研究地点中标准化血液，存储和测量方案， 1）使用国家神经系统疾病和中风研究所相关的公共数据元素 到生物标志物收集，2）正在进行的研究人员培训，3）正在进行的质量控制。具体目标3： 英国广播公司将与行政核心互动，并与成像生物标志物核心和自主教 生物标志物核心确定BBM如何增强PPC的表征并改善了PPC的表征 PPCS预测的准确性通过1）表征与PPCS内表型相关的BBM特异性测量值， 2）分析BBM数据。在该项目结束时，我们不仅会开发PPCS风险分层 实用，可扩展和准确的算法，我们将确定BBMS对PPC的独特贡献 Emas。我们的结果有可能识别潜在的可修改炎症途径并阐明 该年龄段的有症状恢复的生物学机制。