Rapid saliva test for noninvasive diagnostic screening of MCI and dementia

用于 MCI 和痴呆症无创诊断筛查的快速唾液检测

• 批准号: 10652613
• 负责人: Mark Ettenhofer
• 金额: $ 130.22万
• 依托单位: GAIA MEDICAL INSTITUTE, LLC
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10652613
• 关键词: Accounting; Adoption; Age; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease care; Alzheimer' s disease diagnosis; Alzheimer’s disease biomarker; American; Biological; Biological Assay; Biological Markers; Buffers; Characteristics; Chronic; Classification; Clinical; Clinical Data; Cognitive; Cohort Studies; Cost Savings; Cost of Illness; Data; Dementia; Devices; Diagnosis; Diagnostic; Diagnostic tests; Disease; Disease Progression; Dose; Early Diagnosis; Early treatment; Education; Elderly; Enrollment; Evaluation; Female; General Population; Geography; Goals; Guidelines; Health; Health Care Costs; Health Services Accessibility; Human; Immunoassay; Lateral; Legal patent; Life; Measures; Methods; Modeling; Neurocognitive; Neuropsychology; Normal Range; Outcome; Participant; Pathway interactions; Performance; Phase; Race; Risk; Saliva; Sample Size; Sampling; Sensitivity and Specificity; Services; Site; Small Business Innovation Research Grant; Specificity; Specimen; Standardization; Statistical Models; Technology; Testing; Training; Translating; United States National Institutes of Health; Validation; biomarker selection; biomarker validation; burden of illness; candidate marker; clinical care; cohort; community setting; cost; cost effective; demographics; design; diagnostic accuracy; diagnostic biomarker; diagnostic screening; digital; disease phenotype; economic cost; human subject; innovation; lateral flow assay; machine learning method; male; mild cognitive impairment; noninvasive diagnosis; phase 2 study; point of care; point of care testing; prototype; response; rho; saliva sample; salivary assay; screening; sex; statistical and machine learning

Project Summary Rapid saliva test for noninvasive diagnostic screening of MCI and dementia In 2020, over 6.2 million Americans had dementia costing the nation $355 billion. There is unmet need for a standardized, cost-effective test for diagnostic screening of Mild cognitive impairment (MCI) and Alzheimer’s disease (AD) to move towards early detection and treatment of dementia to reduce disease burden and costs. The goal of this SBIR project is to develop a rapid saliva test for diagnosis of MCI and AD. Phase I showed feasibility of key innovations: standardized saliva methods, validated biomarker assays, 10 candidate biomarkers of MCI and AD and a new saliva cartridge for commercial Lateral Flow Immunoassay (LFA). The proposed Phase II study will clinically validate a diagnostic biomarker of MCI and AD biomarker in older adults and develop a prototype device to show feasibility of the commercial product. SA1 will enroll N=400 males and females age ≥50 at 2 sites: N=200 AD, N=100 MCI and N=100 cognitively normal controls (CN). Participants will be assigned to the cohorts based on a gold standard clinical and neurocognitive evaluation. The cohorts will be matched on important demographics and clinical characteristics. The proposed sample size is estimated to provide ≥80% statistical power with 95% error margin. N=550 saliva samples will be collected: 1 sample from all AD, MCI and 70 CN and 6 serial samples from 30 CN. SA2 will measure the 10 candidate biomarkers in N=550 saliva samples from SA1. Statistical modeling of Training set (N=300) will utilize both statistical and machine learning methods to select a composite biomarker and a cutoff based on diagnostic performance for MCI and AD. Potential demographic and clinical covariates will be included in the statistical model. The selected biomarker and cutoff will be validated using clinically and demographically matched Validation set (N=100) based on targeted milestones for diagnostic accuracy, sensitivity and specificity. Serial samples from CN will define the normal range of biomarker concentration and biological variability. SA3 will demonstrate a prototype LFA device for the MCI-AD biomarker validated in SA2. Expected Outcomes: Results of the Phase II study will rigorously clinically validate a new saliva biomarker for diagnosis of MCI and AD. Large and representative sample size (400 subjects across MCI and AD phenotype and stage, age, sex and geography) will provide statistically significant, generalizable clinical data. Standardized preanalytical saliva handing and analytically validated assays will provide accurate and reliable biomarker data. Prototype device will show technical feasibility of the commercial test. Overall, this project has a high potential for a wide-ranging impact on clinical AD care by providing an objective, noninvasive and clinically feasible biological biomarker for diagnosis of AD and MCI, and translating this innovation into a standardized, scalable and cost-effective point- of-care (POC) test for routine dementia screening in the general population. The proposed product has a strong commercial potential based on a proven and low risk LFA device with known and achievable FDA path, competitive patent portfolio, limited competition and key opinion leaders committed to clinical adoption.

项目摘要 快速唾液检测用于 MCI 和痴呆症的无创诊断筛查 2020 年，超过 620 万美国人患有痴呆症，国家损失达 3550 亿美元，但这一需求尚未得到满足。 用于轻度认知障碍 (MCI) 和阿尔茨海默病诊断筛查的标准化、经济高效的测试 疾病（AD）走向痴呆症的早期发现和治疗，以减轻疾病负担和费用。 该 SBIR 项目的目标是开发一种快速唾液测试，用于诊断 I 期 MCI 和 AD。 关键创新的可行性：标准化唾液方法、经过验证的生物标志物检测、10 种候选药物 MCI 和 AD 的生物标志物以及用于商业侧流免疫测定 (LFA) 的新型唾液盒。 拟议的 II 期研究将在老年人中临床验证 MCI 和 AD 生物标志物的诊断生物标志物 并开发原型设备以展示商业产品的可行性 SA1 将招募 N=400 名男性和 2 个地点年龄≥50 岁的女性：N=200 AD、N=100 MCI 和 N=100 认知正常对照 (CN)。 将根据金标准临床和神经认知评估分配到队列。 将根据重要的人口统计数据和临床特征进行估计。 为了提供 ≥80% 的统计功效和 95% 的误差范围，将收集 N=550 个唾液样本：1 个样本。 来自所有 AD、MCI 和 70 个 CN 的样本以及来自 30 个 SA2 的 6 个系列样本将测量 10 个候选生物标志物。 SA1 的 N=550 个唾液样本中的训练集 (N=300) 的统计建模将同时利用统计和模型。 机器学习方法来选择复合生物标志物和基于诊断性能的截止值 MCI 和 AD 可能包含在统计模型中。 选定的生物标志物和截止值将使用临床和人口统计匹配的验证集进行验证 (N=100) 基于连续样本的诊断准确性、敏感性和特异性的目标里程碑。 CN 将定义生物标志物浓度的正常范围，而 SA3 将展示生物变异性。 SA2 中验证的 MCI-AD 生物标记物原型 LFA 设备。 II 研究将对用于诊断 MCI 和 AD 的新唾液生物标志物进行严格的临床验证。 代表性样本量（400 名受试者，涵盖 MCI 和 AD 表型以及分期、年龄、性别和地理位置） 将提供具有统计学意义的、可推广的标准化的分析前唾液处理和数据。 经过分析验证的测定将提供准确可靠的生物标志物数据。原型设备将显示。 总体而言，该项目具有产生广泛影响的巨大潜力。 通过为 AD 治疗提供客观、无创且临床可行的生物标志物，对临床 AD 护理进行研究 AD 和 MCI 的诊断，并将这一创新转化为标准化、可扩展且具有成本效益的点 用于普通人群常规痴呆症筛查的护理 (POC) 测试 拟议产品有一个。 基于经过验证的低风险 LFA 设备以及已知且可实现的 FDA 途径的强大商业潜力， 有竞争力的专利组合、有限的竞争和致力于临床采用的关键意见领袖。