Returning to Everyday Tasks Utilizing Rehabilitation Networks-III Pilot Randomized Clinical Trial (RETURN-III Pilot RCT)

利用康复网络恢复日常任务-III试点随机临床试验（RETURN-III试点RCT）

• 批准号: 10614365
• 负责人: E Wesley ELY
• 金额: --
• 依托单位: VETERANS HEALTH ADMINISTRATION
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10614365
• 关键词: Affect; Air; Alzheimer' s Disease; American; Anatomy; Automobile Driving; Award; Blinded; Brain; Brain Injuries; Caring; Case Series; Cerebrovascular Circulation; Cessation of life; Chronic; Cognition; Cognitive; Critical Illness; Data; Dementia; Diagnosis; Dose; Education; Elderly; Employment; Enrollment; Epidemiology; Episodic memory; Executive Dysfunction; Functional disorder; Funding; Healthcare Systems; Hospitals; Hour; Image; Impaired cognition; Impairment; Incidence; Independent Living; Intensive Care Units; Intervention; Life; Magnetic Resonance Imaging; Measures; Medical; Medication Management; Medicine; Memory; Methods; Neuronal Plasticity; Neuropsychology; Operative Surgical Procedures; Outcome; Patients; Phase; Process; Protocols documentation; Public Health; Randomized; Randomized Clinical Trials; Randomized Controlled Trials; Rehabilitation therapy; Research; Research Personnel; Research Training; Resources; Risk Factors; Severities; Short-Term Memory; Signal Transduction; Structure; Study Section; Surgical Intensive Care; Survivors; Tablets; Technology; Tennessee; Testing; Time; Training Programs; Translating; Traumatic Brain Injury; United States Department of Veterans Affairs; Veterans; Work; active duty; aging brain; arterial spin labeling; base; blood oxygenation level dependent response; brain dysfunction; brain research; cerebral atrophy; clinical center; cognitive rehabilitation; computer game; computerized; effectiveness evaluation; executive function; healing; improved; innovation; novel; portability; primary outcome; processing speed; rehabilitation strategy; survivorship

Of the millions of patients who live through critical illness annually, Intensive Care Unit (ICU) survivorship is marked by a dementia-like brain injury called post-ICU long-term cognitive impairment (ICU-LTCI) that creates grave difficulties with managing medications, handling finances, living independently, and maintaining employment. Data from our group and others show that 50% of ICU survivors suffer from ICU-LTCI and that the number of veterans who develop ICU-LTCI is as high as the number of patients with new traumatic brain injury diagnoses among all Active Duty, National Guard, and Reserves. Our pilot randomized “Returning to Everyday Tasks Utilizing Rehabilitation Networks-I” (RETURN-I) study showed that a 12-week cognitive rehabilitation intervention (versus controls) improved executive dysfunction. We then transformed this non-computerized resource- intensive strategy into a novel, efficient, and scalable Computerized Cognitive Rehabilitation (CCR) approach. This plasticity-based adaptive CCR was applied to ICU survivors enrolled in our uncontrolled case-series (RETURN-II) that signaled improvements across multiple cognitive domains. Building on nearly two decades of aging brain research with the VA-Tennessee Valley Healthcare System Geriatric Research, Education and Clinical Center (VA-TVHS GRECC), we propose this randomized controlled trial to investigate the efficacy of CCR for survivors with ICU- LTCI. The RETURN-III Study will be the next logical data-driven approach to create real-world solutions for Veterans and civilians surviving critical illness with disabling ICU-LTCI. The RETURN-III Study will test the hypotheses that a 12-week CCR intervention in medical and surgical ICU survivors will reduce the severity of cognitive impairment (Aim 1), and result in Magnetic Resonance Imaging (MRI) changes of decreased brain atrophy, greater functional connectivity, and greater cerebral blood flow (Exploratory Aim 2). To test these hypotheses, the RETURN-III study will randomize 160 medical and surgical VA ICU survivors with documented ICU-LTCI up to 14 days post-hospital discharge to either 12-weeks of intervention using CCR (n=80) vs. control of non-specific computer games (n=80). At 3, 6, and 12 months post-randomization, trained research personnel blinded to group assignment will use a validated battery to assess global cognition [primary outcome] (Aim 1: domains of processing speed, working memory, episodic memory, executive function), and to investigate 12-month MRI imaging metrics [exploratory outcome] (Aim 2: standard structural and anatomic protocols, baseline blood oxygenation level dependent responses, pseudo-continuous arterial spin labeling).

在每年数百万患有危重病的患者中，重症监护室（ICU） 生存的标志是痴呆样的脑损伤，称为ICU后长期认知障碍 （ICU-LTCI）在管理药物、处理财务、生活 独立工作，保持就业。我们小组和其他人的数据显示，50%的ICU患者 幸存者患有ICU-LTCI，并且患有ICU-LTCI的退伍军人人数高达 在所有现役军人中，新诊断为创伤性脑损伤的患者人数， 警卫和预备队。我们的试点随机“利用康复回到日常任务 网络-I”（RETURN-I）研究表明，12周的认知康复干预（与 对照组）改善执行功能障碍。然后我们把这个非计算机化的资源- 将集约化策略转化为新型、高效且可扩展的计算机认知康复（CCR） approach.这种基于可塑性的适应性CCR应用于我们的ICU幸存者， 非对照病例系列（RETURN-II），表明多个认知领域的改善。 基于与VA-田纳西流域近二十年的大脑老化研究， 医疗保健系统老年研究，教育和临床中心（VA-TVHS GRECC），我们 我建议进行这项随机对照试验，以研究CCR对ICU幸存者的疗效- LTCI。RETURN-III研究将是下一个逻辑数据驱动的方法， 为退伍军人和平民提供解决方案，帮助他们在重症疾病中幸存下来，并禁用ICU-LTCI。 RETURN-III研究将测试12周CCR干预治疗的假设， 和外科ICU幸存者将降低认知障碍的严重程度（目标1），并导致 磁共振成像（MRI）显示脑萎缩减少，功能增强 连通性和更大的脑血流量（探索性目标2）。 为了检验这些假设，RETURN-III研究将随机抽取160例内科和外科VA 出院后14天内记录ICU-LTCI的ICU幸存者， 使用CCR的干预（n=80）与非特定计算机游戏的控制（n=80）。在3，6，和12 随机分组后3个月，对分组设盲的经过培训的研究人员将使用 经验证的成套测验，用于评估整体认知[主要结局]（目标1：处理领域 速度、工作记忆、情景记忆、执行功能），并研究12个月的MRI 成像指标[探索性结局]（目标2：标准结构和解剖方案，基线 血氧水平依赖性反应，伪连续动脉自旋标记）。