NAPS2 Clinical Core

摘要：NAPS 2临床核心 北美RBD前驱Synculeinopathy联盟，第2阶段（NAPS 2）方案 代表了一个扩大和综合的国际研究财团，专注于RBD，涉及八个 核心和一个项目。NAPS 2旨在大幅和全面增加纵向 临床和生物标志物（血液、CSF、PSG、MRI、DaTscan）数据将可用于RBD研究， 内部和外部研究人员，目标是最终促进疾病修饰的发展， 靶向RBD患者的治疗，以延迟或预防明显的DLB、PD或MSA的发展。当前 NAPS方案（R34 AG 056639，以下简称NAPS 1）是一项为期2年的临床试验计划资助，已成功 在10个研究中心招募了超过200名具有PSG证明的RBD的参与者。一套全面的标准化临床 获得每个参与者的神经认知测量，包括国家阿尔茨海默氏症 协调中心（NACC）统一数据集版本3，路易体痴呆模块和其他特定的 与PD和MSA更相关的措施。生物流体样本，包括DNA和血浆上的所有，和CSF上的一个 子集，已在国家阿尔茨海默氏症集中储存库收集，转移和处理 疾病和相关痴呆症（NCRAD）。这些数据有助于关键的遗传和生物流体标记， 与RBD有关，需要进一步调查。来自NAPS 1的PSG数据已被 集中分析，现在开发了无张力的REM睡眠定量测量; PSG将被 在NAPS 2中进行，关键数据将上传到国家睡眠研究资源（NSRR）。那里 没有足够的资金在NAPS 1的所有研究中心进行神经影像学研究，但MRI和 在一些中心收集的DaTscan成像数据产生了有希望的初步发现，并建立了 将成像纳入NAPS 2的基础;这些扫描将上传到 神经影像学（LONI）。NAPS 2临床核心将建立在NAPS 1计划的明显成功的基础上， 招募大量RBD参与者（N>300），并每年对他们进行全面评估， 标准化的方式。还将评估年龄和性别匹配的健康对照的较小队列， 对特定岩心和项目进行比较分析。前驱期突触核蛋白病评定量表 还将开发用于RBD相关研究和临床试验的药物。为了更广泛地传播 人口筛查和评估，一些新的虚拟和数字措施，在选择RBD患者， 将进行试点。还将为所有RBD参与者寻求尸检的高级指令。临床 因此，核心将获得高质量的临床数据、生物液体样本、PSG数据以及MRI和DaTscan 成像数据将被整合用于所有核心和项目，并与科学界共享， 并探索更多的分析，以期待未来的疾病改善临床试验。

ABSTRACT: NAPS2 CLINICAL CORE The North American Prodromal Synculeinopathy Consortium for RBD, Stage 2 (NAPS2) protocol represents an expanded and integrated international research consortium focused on RBD involving eight cores and one project. NAPS2 is designed to substantially and comprehensively increase the longitudinal clinical and biomarker (blood, CSF, PSG, MRI, DaTscan) data that will be available for research of RBD by internal and external investigators, with the goal of ultimately fostering the development of disease-modifying therapies targeting those with RBD to delay or prevent the development of overt DLB, PD or MSA. The current NAPS protocol (R34 AG056639, hereafter NAPS1) is a 2-year clinical trial planning grant that has successfully enrolled >200 participants with PSG-proven RBD across 10 sites. A comprehensive standardized set of clinical and neurocognitive measures is obtained for each participant, and includes the National Alzheimer’s Coordinating Center (NACC) Uniform Data Set Version 3, the Lewy Body Dementia Module and other specific measures more relevant to PD and MSA. Biofluid samples that include DNA and plasma on all, and CSF on a subset, have been collected, transferred and processed at National Centralized Repository for Alzheimer's Disease and Related Dementias (NCRAD). These data contribute to key genetic and biofluid markers that have been associated with RBD and that warrant further investigation. The PSG data from NAPS1 have been analyzed centrally, with REM sleep without atonia quantitative measures now developed; PSGs will be performed in NAPS2 and key data will be uploaded to the National Sleep Research Resource (NSRR). There was insufficient funding to perform neuroimaging studies across all of the sites in NAPS1, but MRI and DaTscan imaging data collected at a few of the centers resulted in promising preliminary findings and establish the basis for the inclusion of imaging in NAPS2; these scans will be uploaded to the Laboratory of Neuroimaging (LONI). The NAPS2 Clinical Core will build on the obvious success of the NAPS1 program by recruiting a large cohort of RBD participants (N>300) and evaluating them annually in a comprehensive and standardized manner. A smaller cohort of age- and sex-matched healthy controls will also be evaluated for comparative analyses in specific Cores and for the Project. The Prodromal Synucleinopathy Rating Scale for use in RBD-related research and clinical trials will also be developed. In anticipation for more widespread population screening and assessment, some novel virtual and digital measures in select RBD patients and controls will be piloted. Advanced directive for autopsy will also be sought for all RBD participants. The Clinical Core will therefore acquire high quality clinical data, biofluid samples, PSG data, and MRI and DaTscan imaging data to be integrated for use in all Cores and the Project and shared with the scientific community, as well as explore additional analyses in anticipation of future disease-modifying clinical trials.