Alzheimer's Prevention Initiative APOE4 Trial

阿尔茨海默病预防计划 APOE4 试验

• 批准号: 8605297
• 负责人: ERIC MICHAEL REIMAN
• 金额: $ 3326.02万
• 依托单位: BANNER ALZHEIMER'S INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8605297
• 关键词: Age; Alzheimer disease prevention; Alzheimer' s Disease; Alzheimer' s disease risk; Amyloid; Apolipoprotein E; Biological; Biological Markers; Brain imaging; Cerebrospinal Fluid; Cerebrum; Clinical; Clinical Trials Data Monitoring Committees; Clinical Trials Design; Cognitive; Communities; Complement; Complement component C6; Data; Development; Disclosure; Elderly; Elements; Enrollment; European; Evaluation; Funding; Futility; Future; Genes; Genetic; Genetic screening method; Genotype; Glucose; Goals; Health; Heterozygote; Homozygote; Individual; Industry; Investigational Therapies; Late Onset Alzheimer Disease; Lead; Licensing; Magnetic Resonance Imaging; Measurement; Measures; Medicine; Metabolic; Methods; Motivation; Outcome; Participant; Persons; Pharmacologic Substance; Philanthropic Fund; Placebo Control; Placebos; Policies; Positron-Emission Tomography; Prevention Research; Prevention therapy; Procedures; Qualifying; Randomized; Randomized Clinical Trials; Registries; Request for Proposals; Research; Research Infrastructure; Resources; Risk; Safety; Sampling; Series; Specific qualifier value; Staging; Surrogate Endpoint; Symptoms; Testing; Therapeutic; Therapy Clinical Trials; Time; United States National Institutes of Health; Widespread Disease; Work; base; brain volume; clinical effect; clinical risk; cognitive change; disease-causing mutation; effective therapy; fight against; fluorodeoxyglucose positron emission tomography; genetic risk factor; meetings; mutation carrier; pre-clinical; preclinical evaluation; preclinical study; prevent; primary outcome; programs; response; tau Proteins; theories; treatment effect; trend; uptake

DESCRIPTION: The Alzheimer's Prevention Initiative (API) was established to rapidly evaluate investigational preclinical Alzheimer's disease (AD) treatments in cognitively unimpaired people who, based on their genetic background and age, are at the highest imminent risk for clinical progression, to help advance a new era in AD prevention research, and to find treatments that work as soon as possible. This application seeks five years of partial support for the initial stag of a 104-260 week multi-center randomized clinical trial of an investigational amyloid-¿ (A¿) modifying treatment in 650 cognitively unimpaired 60-75 year-old apolipoprotein E (APOE) ¿4 homozygotes (HMs) using the best established cognitive, brain imaging and cerebrospinal fluid (CSF) measurements of preclinical AD. The primary outcome is change in an empirically predefined composite cognitive test score. Other outcomes include changes in volumetric magnetic resonance imaging (MRI), fluorodeoxyglucose positron emission tomography (FDG PET) regional cerebral metabolic rate for glucose (rCMRgl), flutemetamol PET fibrillar A¿, and CSF A¿42, total tau (t-tau) and phospho-tau (p-tau) measurements. Adaptive elements include serial futility assessments, a 104-week interim analysis, and data and safety monitoring board (DSMB)-facilitated decisions about study continuation, study expansion, and the evaluation of other at-risk groups. Exploratory analyses will determine whether the treatment's 24-month treatment effects are related to the treatment's clinical effects and whether biomarker evidence of less extensive disease is associated with a greater therapeutic response. This study complements API's funded trial in autosomal dominant AD (ADAD) mutation carriers. It capitalizes on our longstanding efforts to characterize the preclinical biomarker and cognitive changes in APOE ¿4 HM, heterozygotes (HTs) and noncarriers (NCs), several of the API's established policies, procedures, and collaborative relationships, its data and sample-sharing paradigm and growing Alzheimer's Prevention Registry, and at least $50 million in additional industry and philanthropic funding. Our potentially license-enabling APOE ¿4 and ADAD mutation carrier trials have been vetted by leading academic, industry, NIA, regulatory agency, and community stakeholders. The project's aims: to evaluate an investigational A¿-modifying treatment in unimpaired HMs, to provide a better test of the amyloid hypothesis, to determine whether to evaluate the treatment in others at risk for late-onset AD, to help clarify the extent t which a treatment's biomarker effects may predict a clinical response and qualify as "reasonably likely" surrogate endpoints in future preclinical trials, to provide information about the impact o APOE genetic test disclosure in this new era of AD prevention research, to provide a public resource of data and samples after the trial is over, and to complement and support other research programs related to the evaluation of preclinical AD treatments. The project is intended to help find effective preclinical treatments for late-onset AD as soon as possible.

描述：建立了阿尔茨海默氏症的预防倡议（API），以迅速评估研究性临床前阿尔茨海默氏病（AD）治疗（AD）在认知单pirip的人中，基于他们的遗传背景和年龄，他们处于临床进展的最高风险，以帮助您在Ad Pricention Itherection中促进新的治疗，并尽可能快地进行临床进展。该申请寻求为期五年的部分支持，以对一项104-260周的多中心多中心随机临床试验的初始鹿角进行了研究淀粉样蛋白 - （a¿）修改治疗的650次认知未经损害的60-75岁的载脂蛋白E（apoE）E（apoE）的治疗方法使用了最佳的固定型（HMS（HMS））。临床前AD的测量。主要结果在经验预定义的复合认知测试评分中发生了变化。其他结果包括变化的体积磁共振成像（MRI），葡萄糖（RCMRGL）的荧光氧合葡萄糖阳性发射断层扫描（FDG PET）区域脑代谢率，flutemetamol pet fibrelara¿自适应元素包括串行能源评估，104周的临时分析以及数据与安全监测委员会（DSMB）关于研究延续，研究扩展以及对其他高危群体的评估的促进决策。探索性分析将确定治疗的24个月治疗效果是否与治疗的临床效应以及较不宽泛的疾病的生物标志物证据是否与更大的热反应有关。这项研究符合API在常染色体显性AD（ADAD）突变载体中的资助试验。它利用了我们的长期努力来表征APOE的临床前生物标志物和认知变化。4HM，杂合子（HTS）和非驾驶员（NCS）（NCS），API的几种建立的政策，程序，程序和协作关系，其数据和样品共享的态度和额外的alzheimer和$ 50属于Alzheimer的prepention和$ 50的prepention Remistion，以及$ 50资金。我们可能获得许可的APOE„ 4和ADAD突变载体试验已由领先的学术，行业，NIA，监管机构和社区利益相关者审查。 The project's aims: to evaluate an investment -modifying treatment in unipaired HMs, to provide a better test of the amyloid hypothesis, to determine whether to evaluate the treatment in others at risk for late-onset AD, to help clarify the extent t which a treatment's biomarker effects may predict a clinical response and qualify as "reasonably likely" surrogate endpoints in future preclinical trials, to provide information about the impact o APOE genetic test disclosure在这个新的预防研究时代，在试验结束后提供了数据和样本的公共资源，并补充和支持与临床前广告处理评估有关的其他研究计划。该项目旨在帮助尽快找到晚发广告的有效临床前治疗。