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.

项目摘要 基于越来越多的人认识到阿尔茨海默病(AD)的漫长痴呆前期阶段代表着 旨在修改疾病神经生物学、最新药物开发的干预措施的最佳时间 该计划招收临床前/无症状和前驱/轻度认知障碍阶段的参与者。 然而，招聘过程和现场激活的时间框架、复杂性和费用 二级预防试验极具挑战性，而且确实是现场启动和试验登记，总的来说， 是AD药物开发的最大瓶颈。因此，我们这个领域越来越多的共识是 我们必须从根本上彻底改革目前的临床试验招募和评估程序，以便及早 干预试验。这项提案的首要目标是加速当前和未来的二级预防 通过创新、高效的方法进行试用登记，以确定、评估和登记适当 临床前和先兆试验候选者，由一个新的站点网络支持，该网络增强了对更多 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)试验的就绪队列(TRC-PAD)。TRC-PAD(n=2000；1000 临床前/1000先兆AD)将促进使用ACTC框架进行的PAD试验的登记。这 应用程序描述了将现有的“供给器”注册表和研究连接到基于Web的注册表的过程，以 获取老年人、非痴呆者的人口统计、遗传和纵向临床及认知信息 对试验感兴趣的个人。注册表数据为AD病理生成风险分数(最初为高 大脑中的淀粉样蛋白，但具有适应tau病理和其他生物标志物的方法)，这使得高效 选择面对面生物标记物(最初是淀粉样蛋白PET扫描)和临床评估的候选者。这个 这些评估的结果反过来又允许自适应统计算法来改进选择过程 继续前进。PET扫描显示淀粉样蛋白在大脑中积聚(或替代生物标记物)的个人 确认)被邀请加入预合格临床网络内的半年一次的面对面随访 网站，他们可以从那里被邀请注册参加早期试验。总体而言，这一过程将大大缩短 临床前/先兆试验的时间表，并将解决一系列科学假设，以指导进一步 该领域的发展。