Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's Disease

临床前/前驱阿尔茨海默病的试验就绪队列

• 批准号: 9885998
• 负责人: Paul S. Aisen
• 金额: $ 492.96万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2023-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9885998
• 关键词: Address; Algorithms; Alzheimer disease screening; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer’s disease biomarker; American; Amyloid; Amyloid beta-42; Amyloid beta-Protein; Biological Assay; Biological Markers; Brain; Clinical; Clinical Research; Clinical Trials; Clinical assessments; Cognitive; Collaborations; Collection; Communities; Consensus; Consent; Country; Data; Data Collection; Dementia; Development; Disease; Early intervention trials; Eligibility Determination; Enrollment; Freezing; Future; Genetic; Goals; Home environment; Immunoassay; Immunoprecipitation; Impaired cognition; Individual; Insurance; Internet; Intervention; Life; Mass Spectrum Analysis; Measurement; Measures; Medical; Methods; Nerve Degeneration; Neurobiology; Observational Study; Online Systems; Outcome Measure; Participant; Pathology; Pathway interactions; Performance; Persons; Pharmacy facility; Plasma; Positron-Emission Tomography; Prevention trial; Process; Process Assessment; Program Development; Registries; Reporting; Risk; Sampling; Scientist; Secondary Prevention; Sensitivity and Specificity; Series; Ships; Site; Specimen; Spinal Puncture; Statistical Algorithm; Stream; System; Technology; Testing; Time; TimeLine; Travel; Validation; Work; apolipoprotein E-4; base; candidate selection; clinical biomarkers; clinical research site; cognitive function; cognitive performance; cognitive testing; cohort; cost; data registry; demographics; drug development; experience; follow-up; functional outcomes; health care settings; health data; high risk; improved; innovation; interest; mild cognitive impairment; neuroimaging; non-demented; novel; pre-clinical; prodromal Alzheimer' s disease; recruit; tau Proteins; tool

Project Summary Based on growing recognition that the long pre-dementia stages of Alzheimer's disease (AD) represent the optimal time for interventions aimed at modifying the neurobiology of the disease, most recent drug development programs enroll participants at the preclinical/asymptomatic and prodromal/mild cognitive impairment stages. However, the timeframe, complexity and expense of the recruitment process and site activation for these secondary prevention trials are extremely challenging, and indeed site start-up and trial enrollment, in general, represent the greatest bottleneck for drug development for AD. Thus, there is growing consensus in our field that we must fundamentally overhaul the current clinical trial recruitment and assessment process for these early intervention trials. The overarching goal of this proposal is to accelerate current and future secondary prevention trial enrollment through an innovative, highly efficient approach to identify, evaluate, and enroll appropriate preclinical and prodromal trial candidates, supported by a new site network with enhanced capacities for more efficient and effective conduct of AD clinical trials. The specific goal of the current project is to build a large trial- ready cohort (TRC) for preclinical/prodromal AD (PAD) trials (TRC-PAD). TRC-PAD (n=2000; 1000 preclinical/1000 prodromal AD) will facilitate enrollment into ongoing PAD trials using the ACTC framework. This application describes a process of connecting existing “feeder” registries and studies to a web based Registry to capture demographic, genetic and longitudinal clinical and cognitive information on older, non-demented individuals interested in trials. The Registry data generates risk scores for AD pathology (initially elevated amyloid in brain, but with methods adaptable to tau pathology and other biomarkers), that allows efficient selection of candidates for in-person biomarker (initially amyloid PET scans) and clinical assessment. The results of these assessments, in turn, allow an adaptive statistical algorithm to improve the selection process moving forward. Individuals with PET scans showing amyloid accumulation in brain (or alternative biomarker confirmation) are invited to join with semi-annual in-person follow-up within the network of pre-qualified clinical sites, from which they can be invited to enroll in early stage trials. Overall, the process will dramatically shorten the timeline for preclinical/prodromal trials, and will address a series of scientific hypotheses to guide further development in the field.

项目概要 人们越来越认识到阿尔茨海默病 (AD) 的长期痴呆前期代表了 旨在改变疾病神经生物学、最新药物开发的干预措施的最佳时间 计划招收临床前/无症状和前驱/轻度认知障碍阶段的参与者。 然而，这些项目的招聘流程和网站激活的时间安排、复杂性和费用 二级预防试验极具挑战性，实际上，总体而言，现场启动和试验注册， 是 AD 药物开发的最大瓶颈，因此，我们领域越来越达成共识： 我们必须从根本上彻底改革当前的临床试验招募和评估流程 该提案的总体目标是加速当前和未来的二级预防。 通过创新、高效的方法来识别、评估和招募合适的试验注册 临床前和前驱试验候选者，得到新站点网络的支持，该网络具有增强的能力，可以提供更多 高效、有效地开展 AD 临床试验 当前项目的具体目标是建立一个大型试验- 临床前/前驱 AD (PAD) 试验就绪队列 (TRC) (TRC-PAD)（n=2000；1000）。 临床前/1000 前驱期 AD）将有助于使用 ACTC 框架参加正在进行的 PAD 试验。 应用程序描述了将现有“馈送”注册和研究连接到基于网络的注册的过程 捕获老年人、非痴呆患者的人口统计、遗传、纵向临床和认知信息 对试验感兴趣的个人。注册数据生成 AD 病理学的风险评分（最初升高）。 大脑中的淀粉样蛋白，但采用适合 tau 病理学和其他生物标志物的方法），这使得有效 选择现场生物标志物候选者（最初是淀粉样蛋白 PET 扫描）和临床评估。 这些评估的结果反过来又允许自适应统计算法改进选择过程 PET 扫描显示大脑中淀粉样蛋白积累（或替代生物标志物）的个体。 确认）被邀请参加资格预审临床网络内每半年一次的现场随访 总体而言，该过程将大大缩短。 临床前/前驱试验的时间表，并将提出一系列科学假设以进一步指导 领域的发展。