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: 10326264
• 负责人: Robert J Elbin
• 金额: $ 86.6万
• 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 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10326264
• 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; 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 快速唾液检测对脑震荡后持续症状的诊断和预后 （PPCS）儿童和成人 轻度创伤性脑损伤（mTBI）是死亡率和发病率的主要原因。儿童的风险更高 因为未成熟的大脑极易受到创伤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），阻止其重返工作岗位， 学校和体育由于缺乏标准，目前mTBI和PPCS的诊断方法不准确 诊断标准客观生物标志物检测的需求尚未得到满足。SBIR项目的最终目标是 开发用于mTBI诊断和PPCS预后的商业唾液测试。第一阶段表明， 关键创新：用于儿童和成人mTBI诊断和PPCS预后的唾液生物标志物。的 拟议的II期研究旨在临床验证商业测试的最终生物标志物，并开发一种 展示商业产品可行性的原型装置。SA 1将采集N=465份连续唾液样本 来自N=225名11-21岁的青少年运动员，在一项mTBI、骨科 损伤对照（OI）和健康对照（HC）。mTBI在伤后≤ 72 h诊断，PPCS在伤后30 d诊断。 将在mTBI损伤后≤ 72 h、7 d和14 d以及入组表OI和HC时采集唾液样本。 拟定的样本量将提供>80%的统计功效，以获得统计学上显著的生物标志物数据。 SA 2将测量N=1063个唾液样品中的5个候选生物标志物（N=465个来自SA 1的样品加上N=598个 来自艾德患者和成年运动员的现有样品）。一组训练对象的统计建模 （N=475）将根据最佳诊断和 预测性能将使用验证集（N=240）对选定的标志物和终点进行验证 基于儿童mTBI诊断和PPCS预后的准确性、敏感性和特异性≥90%， 成年人了OI将显示mTBI特异性。HC将定义标志物浓度和生物学的正常范围 可变性SA 3将为选定的生物标志物开发原型侧流免疫测定（LFA）。预计 结果：结果将在临床上严格验证mTBI和PPCS的唾液生物标志物， 商业产品。具有代表性的大样本量（N=715例受试者， 损伤、结果、年龄、性别和地理位置）将提供统计学上显著的、可推广的临床数据。 N=1063份连续唾液样本和经分析验证的测定将提供准确可靠的生物标志物 数据该原型装置将展示商业测试的技术可行性。总的来说，这个项目有很高的 通过提供客观的、临床上可行的生物学方法， mTBI和PPCS的生物标志物，并将这一创新转化为临床应用的实用工具， 在乎申报产品基于经验证的低风险LFA器械，具有很强的商业潜力， 可实现的FDA路径，致力于临床采用的关键意见领袖，有竞争力的专利组合， 有限的竞争。