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 基于日益认识到阿尔茨海默氏病（AD）的长期前痴呆前阶段代表 旨在修改该疾病神经生物学的干预措施的最佳时间，最新的药物开发 计划参与者参加临床前/无症状和前驱/轻度认知障碍阶段的计划。 但是，招聘过程的时间范围，复杂性和费用和这些现场激活 二级预防试验极为挑战，实际上，现场启动和试验入学率通常 代表了AD药物开发的最大瓶颈。那就是我们领域越来越多的共识 我们必须从根本上大修这些早期的当前临床试验招聘和评估过程 干预试验。该提案的总体目标是加速当前和未来的二级预防 通过一种创新，高效的方法进行试用，以识别，评估和注册适当 临床前和前驱试验候选人，由新的站点网络支持，具有增强的能力 AD临床试验的有效有效行为。当前项目的具体目标是建立大型试验 - 用于临床前/前驱AD（PAD）试验（TRC-PAD）的Ready COHORT（TRC）。 trc-pad（n = 2000; 1000 临床前/1000个前驱AD）将有助于使用ACTC框架进行正在进行的PAD试验。这 应用程序描述了将现有的“馈线”注册表和研究与基于Web的注册表连接到的过程 捕获有关较老的，不痴呆的人口统计学，遗传和纵向临床和认知信息 对试验感兴趣的人。注册表数据产生了AD病理学的风险评分（最初升高） 大脑中的淀粉样蛋白，但具有适应于tau病理学和其他生物标志物的方法），可以有效 选择面对面生物标志物（最初是淀粉样蛋白PET扫描）和临床评估的候选者。这 这些评估的结果反过来允许自适应统计算法改善选择过程 前进。患有PET扫描的个体显示淀粉样蛋白在大脑中的积累（或替代生物标志物 邀请确认）与预先合格的临床网络中的半实间人亲自进行随访 可以邀请他们参加早期试验的网站。总体而言，该过程将大大缩短 临床前/前驱试验的时间表，并将介绍一系列科学假设，以进一步指导 该领域的发展。