Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer's disease
Deep and Frequent Phenotyping study protocol: an observational study in prodromal Alzheimer's disease
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DOI：
10.1136/bmjopen-2018-024498
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发表时间：
2019-06-01
期刊：
影响因子：
2.9
通讯作者：
Lovestone, Simon
中科院分区：
文献类型：
--
作者：
Koychev, Ivan;Lawson, Jennifer;Lovestone, Simon
介绍最近失败的潜在新的治疗阿尔茨海默氏病（AD），促使临床研究的前驱或临床前状态。然而，在疾病的早期阶段进行临床试验是极具挑战性的一个关键原因是不可行的使用经典的结果措施的痴呆症试验（如，转换为痴呆症）和缺乏有效的替代措施，所以在疾病的早期过程。深度和频繁表型（DFP）研究旨在通过鉴定一组标记物来解决这个问题，所述标记物在疾病的前驱期中作为疾病进展的指标，其可以在概念验证试验中用作指示性结果测量。方法和分析DFP研究是重复测量观察性研究，其中参与者将通过现有的父母队列、研究兴趣列表/数据库、广告和记忆诊所将对已建立的（认知、正电子发射断层扫描（PET）成像或脑脊液（CSF）病理学标志物、神经变性的结构MRI标志物）和实验模式（功能性MRI、脑磁图和/或脑电图、步态测量、眼科和基于连续智能手机的认知和其他评估以及实验性CSF、血液、泪液和唾液生物标志物）进行重复测量。我们将招募年龄>60岁的前驱AD男性和女性参与者，前驱AD定义为没有痴呆但具有认知障碍的证据以及使用PET成像或CSF生物标志物评估的AD病理学。没有AD病理学证据的对照参与者将以1：4的比例纳入。伦理和传播该研究获得了South Central-Oxford B NHS研究伦理委员会的有利伦理意见（REC参考17/SC/0315;于2017年8月18日批准; 2018年2月13日修订）。数据将在研究和数据收集完成后1年内与科学界共享。
Introduction Recent failures of potential novel therapeutics for Alzheimer's disease (AD) have prompted a drive towards clinical studies in prodromal or preclinical states. However, carrying out clinical trials in early disease stages is extremely challenging-a key reason being the unfeasibility of using classical outcome measures of dementia trials (eg, conversion to dementia) and the lack of validated surrogate measures so early in the disease process. The Deep and Frequent Phenotyping (DFP) study aims to resolve this issue by identifying a set of markers acting as indicators of disease progression in the prodromal phase of disease that could be used as indicative outcome measures in proof-of-concept trials.Methods and analysis The DFP study is a repeated measures observational study where participants will be recruited through existing parent cohorts, research interested lists/databases, advertisements and memory clinics. Repeated measures of both established (cognition, positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) markers of pathology, structural MRI markers of neurodegeneration) and experimental modalities (functional MRI, magnetoencephalography and/or electroencephalography, gait measurement, ophthalmological and continuous smartphone-based cognitive and other assessments together with experimental CSF, blood, tear and saliva biomarkers) will be performed. We will be recruiting male and female participants aged >60 years with prodromal AD, defined as absence of dementia but with evidence of cognitive impairment together with AD pathology as assessed using PET imaging or CSF biomarkers. Control participants without evidence of AD pathology will be included at a 1: 4 ratio.Ethics and dissemination The study gained favourable ethical opinion from the South Central-Oxford B NHS Research Ethics Committee (REC reference 17/SC/0315; approved on 18 August 2017; amendment 13 February 2018). Data will be shared with the scientific community no more than 1 year following completion of study and data assembly.