Rapid saliva test for diagnosis of mTBI and prognosis of Persistent Post-conccussion Symptoms (PPCS) in children and adults

快速唾液检测用于诊断儿童和成人 mTBI 以及持续性脑震荡后症状 (PPCS) 的预后

• 批准号: 10490332
• 负责人: Robert J Elbin
• 金额: $ 83.28万
• 依托单位: GAIA MEDICAL INSTITUTE, LLC
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10490332
• 关键词: Accounting; Adolescent; Adoption; Adult; Age; Arkansas; Biological; Biological Assay; Biological Markers; Brain; Brain Concussion; Buffers; Caring; Cause of Death; Child; Clinical; Clinical Data; Data; Devices; Diagnosis; Diagnostic; Diagnostic Procedure; Dose; Emergency Department patient; Enrollment; Geography; Goals; HIF1A gene; Immunoassay; Injury; Laboratories; Lateral; Legal patent; Letters; Logistic Regressions; Measures; Modeling; Morbidity - disease rate; Normal Range; Orthopedics; Outcome; POR gene; Pathway interactions; Patients; Performance; Phase; Post-Concussion Syndrome; Prognosis; Prospective cohort study; Public Health; ROC Curve; Race; Research; Risk; Saliva; Sample Size; Sampling; Schools; Sensitivity and Specificity; Small Business Innovation Research Grant; Specificity; Specimen; Sports; Standardization; Statistical Data Interpretation; Statistical Models; Symptoms; Testing; Time; Training; Translating; Trauma; United States National Institutes of Health; Validation; Visual; Work; base; biomarker validation; candidate marker; cohort; college; design; diagnostic criteria; digital; disability; high risk; high school; innovation; junior high school; lateral flow assay; mild traumatic brain injury; mind control; mortality; phase 2 study; point of care; predictive marker; prevent; prognostic; prognostic performance; prototype; saliva sample; salivary assay; sex; tool

Project Summary Rapid saliva test for diagnosis of mTBI and prognosis of Persistent Post-concussion Symptoms (PPCS) in children and adults Mild traumatic brain injury (mTBI) is a leading cause of mortality and morbidity. Children are at a higher risk due to high vulnerability of the immature brain to trauma. mTBI is a significant public health concern because approximately 30% patients develop Persistent Post-concussion Symptoms (PPCS) preventing return to work, school and sports. Current diagnostic methods for mTBI and PPCS are inaccurate due to lack of standard diagnostic criteria. There is unmet need for objective biomarker test. The ultimate goal of this SBIR project is to develop a commercial saliva test for diagnosis of mTBI and prognosis of PPCS. Phase I showed feasibility of the key innovation: saliva biomarkers for diagnosis of mTBI and prognosis of PPCS in children and adults. The proposed Phase II study aims to clinically validate the final biomarker for the commercial test and develop a prototype device showing feasibility of the commercial product. SA1 will collect N=465 serial saliva samples from N=225 adolescent athletes age 11-21 during a multisite prospective cohort study of mTBI, orthopedic injury controls (OI) and healthy controls (HC). mTBI will be diagnosed at ≤72h and PPCS at 30d postinjury. Saliva samples will be collected at ≤72h, 7d and 14d postinjury from mTBI and at enrollment form OI and HC. The proposed sample size will provide >80% statistical power to obtain statistically significant biomarker data. SA2 will measure 5 candidate biomarkers in N=1063 saliva samples (N=465 samples from SA1 plus N=598 existing samples from ED patients and adult athletes). Statistical modeling of a Training set of subjects (N=475) will down select the final marker and endpoint for the commercial test based on best diagnostic and prognostic performance. The selected marker and endpoint will be validated using a Validation set (N=240) based on ≥90% accuracy, sensitivity and specificity of mTBI diagnosis and PPCS prognosis in children and adults. OI will show mTBI specificity. HC will define normal range of marker concentrations and biological variability. SA3 will develop a prototype lateral flow immunoassay (LFA) for a selected biomarker. Expected Outcomes: Results will rigorously clinically validate the saliva biomarker of mTBI and PPCS for the commercial product. Large and representative sample size (N=715 subjects across mTBI mechanisms of injury, outcome, age, sex and geography) will provide statistically significant, generalizable clinical data. N=1063 serial saliva samples and analytically validated assays will provide accurate and reliable biomarker data. The prototype device will show technical feasibility of the commercial test. Overall, this project has high potential for a wide-ranging impact on TBI care by providing an objective, clinically feasible biological biomarker of mTBI and PPCS, and translating this innovation into a practical tool for clinical use in point-of- care. The proposed product has a strong commercial potential based on a proven and low risk LFA device, achievable FDA path, key opinion leaders committed to clinical adoption, competitive patent portfolio and limited competition.

项目摘要 唾液快速检测对脑震荡后遗症的诊断及预后评估 (PPC)在儿童和成人中 轻度创伤性脑损伤(MTBI)是导致死亡和发病的主要原因。儿童面临更高的风险 这是由于未成熟的大脑对创伤的高度脆弱性。MTBI是一个重大的公共卫生问题，因为 大约30%的患者出现持续性脑震荡后症状(PPCS)，阻碍重返工作岗位， 学校和体育。由于缺乏标准，目前对mTBI和PPCS的诊断方法并不准确 诊断标准。客观生物标记物检测的需求尚未得到满足。该SBIR项目的最终目标是 建立一种用于诊断mTBI和PPCS预后的商业化唾液检测方法。第一阶段显示了 关键的创新：唾液生物标记物在儿童和成人中诊断mTBI和PPCS的预后。这个 拟议的第二阶段研究旨在临床验证用于商业测试的最终生物标记物，并开发 展示商业产品可行性的原型装置。SA1将收集N=465个系列唾液样本 来自N=225名年龄在11-21岁的青少年运动员，在一项关于骨科mTBI的多点前瞻性队列研究中 伤害对照组(OI)和健康对照组(HC)。≤在伤后72小时确诊，伤后30天确诊。 唾液样本将在≤伤后72小时、7天和14天从mTBI采集，并在登记表格OI和HC时采集。 拟议的样本量将提供80%的统计能力，以获得具有统计意义的生物标志物数据。 SA2将在N=1063个唾液样本(N=465个来自SA1加上N=598个样本)中测量5个候选生物标志物 现有样本来自ED患者和成年运动员)。一组训练对象的统计建模 (n=475)将根据最佳诊断和 预后表现。所选标记和端点将使用验证集(N=240)进行验证 根据≥90%的准确性、敏感度和特异度对儿童脑外伤的诊断和预后判断。 成年人。OI将显示mTBI的特异性。HC将定义正常的标记物浓度和生物学范围 可变性。SA3将为选定的生物标记物开发一种原型侧向流动免疫分析(LFA)。预期 结果：结果将严格地在临床上验证唾液生物标志物mTBI和PPCS对于 商业产品。大样本量和代表性样本量(N=715名受试者，跨越以下mTBI机制 伤害、结局、年龄、性别和地理位置)将提供具有统计学意义的、可推广的临床数据。 N=1063个系列唾液样本和经过分析验证的化验将提供准确可靠的生物标志物 数据。该原型装置将显示商业测试的技术可行性。总体而言，这个项目有很高的 通过提供一种客观的、临床上可行的生物学方法，可能对脑损伤护理产生广泛的影响 MTBI和PPCS的生物标记物，并将这一创新转化为临床使用的实用工具 关心。基于经过验证的低风险LFA设备，建议的产品具有很强的商业潜力， FDA可实现的途径、致力于临床采用的关键意见领袖、具有竞争力的专利组合和 有限的竞争。