Efficacy and target engagement of a digital intervention to improve the depression-executive dysfunction syndrome after stroke

数字干预改善中风后抑郁-执行功能障碍综合征的功效和目标参与度

• 批准号: 10525426
• 负责人: Abhishek Jaywant
• 金额: $ 19.55万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10525426
• 关键词: Address; Aftercare; Anterior; Antidepressive Agents; Attention; Awareness; Base of the Brain; Brain; Brain Injuries; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Collaborations; Control Groups; Data; Data Analytics; Depressed mood; Digit structure; Educational workshop; Executive Dysfunction; Functional Magnetic Resonance Imaging; Goals; Grant; Impaired cognition; Individual; International; Intervention; Investigational Therapies; K-Series Research Career Programs; Knowledge; Left; Manuscripts; Measures; Mental Depression; Mentors; Mentorship; Modality; Modeling; Montgomery and Asberg depression rating scale; Mood Disorders; Neurosciences; Participant; Patient Self-Report; Patients; Performance; Preparation; Psychological Transfer; Randomized; Research; Research Personnel; Research Proposals; Rest; Role; Self Perception; Short-Term Memory; Side; Social Functioning; Standardization; Stroke; Syndrome; Testing; Time; Training; Treatment Efficacy; Writing; affective disturbance; base; career; career development; cognitive rehabilitation; cognitive testing; cognitive training; comorbidity; daily functioning; depressive symptoms; design; digital intervention; digital treatment; disability; efficacious treatment; efficacy evaluation; executive function; experience; functional MRI scan; functional outcomes; group intervention; improved; improved functioning; multitask; neuroimaging; neuropsychiatry; novel; personalized intervention; post intervention; post stroke; post stroke depression; programs; remote delivery; remote intervention; side effect; skills; stroke patient; stroke rehabilitation; stroke survivor; symposium; targeted treatment; therapeutic target; therapy design; treatment optimization; virtual

Project Summary/Abstract The goal of the proposed K23 Career Development Award is to provide the PI with the mentorship, knowledge, and skillset to develop into an independent investigator studying neuroscience-inspired, targeted therapeutics for comorbid mood and cognitive dysfunction after stroke. The PI's mentoring team will provide him with training in the brain-based mechanisms of mood disorders, use of functional MRI to examine target engagement, and clinical trial design and data analytic approaches. The training will incorporate individualized tutorials, formal coursework, national and international workshops and conferences, research collaboration, manuscript preparation, and grant writing. The training is integrated in a research proposal that evaluates the efficacy and target engagement of a digital intervention for the depression-executive dysfunction syndrome (DED) after stroke. Stroke is a leading cause of disability worldwide. Post-stroke DED is associated with more persistent depressive symptoms and executive dysfunction, worse social functioning, and greater loss of independence than post-stroke depression or executive dysfunction alone. Existing interventions have limited evidence of efficacy, side effects, and can be difficult for stroke patients to access. Novel and scalable approaches that target the mechanisms underlying post-stroke DED may yield more efficacious treatment. To address these barriers, the PI proposes to study a remote intervention for post-stroke DED that combines an iPad-based digital therapy called AKL-T01 that intensively trains rapid multitasking skills, together with virtual metacognitive coaching. AKL-T01 is designed to target a common mechanism underlying post-stroke depressive symptoms and executive dysfunction, which is reduced intrinsic functional connectivity in the executive control network (ECN). Virtual metacognitive coaching is included to address patient unawareness of deficits to enhance transfer of training gains to daily functioning. In this pilot clinical trial, N=70 patients with a first-time stroke and DED will be randomized to receive the intervention, or to a control condition with general and non-targeted cognitive stimulation together with metacognitive coaching. Participants will complete measures of executive dysfunction, depressive symptoms, and disability at baseline, week 3 (mid treatment), and week 6 (end treatment). Participants will complete resting state fMRI scans at baseline and week 6. Linear mixed-effects models will test the hypotheses that the intervention will be associated with greater improvements in executive function, depressive symptoms, and disability relative to the control group. Also tested is the hypothesis that the intervention group will have greater change in intrinsic functional connectivity in the ECN from baseline to week 6, relative to the control group. This project has the potential to address, in a scalable manner, a highly debilitating consequence of stroke. It will generate data that can be used to optimize treatment efficacy, further refine and personalize the intervention, and further validate a target for treatment.

项目概要/摘要 拟议的 K23 职业发展奖的目标是为 PI 提供指导、知识、 培养成为一名独立研究者，研究受神经科学启发的靶向治疗的技能 用于中风后共病情绪和认知功能障碍。 PI 的指导团队将为他提供 基于大脑的情绪障碍机制培训，使用功能性 MRI 检查目标 参与、临床试验设计和数据分析方法。培训将包含个性化 教程、正式课程、国内和国际研讨会和会议、研究合作、 手稿准备和资助写作。该培训被纳入一项研究计划中，该计划评估了 数字干预治疗抑郁-执行功能障碍综合征的功效和目标参与度 (DED) 中风后。中风是全世界残疾的主要原因。中风后 DED 与更多因素相关 持续的抑郁症状和执行功能障碍、社会功能恶化以及更大的丧失 独立性高于中风后抑郁症或单独的执行功能障碍。现有的干预措施有限 疗效、副作用的证据，对于中风患者来说可能很难获得。新颖且可扩展 针对中风后 DED 潜在机制的方法可能会产生更有效的治疗。到 为了解决这些障碍，PI 建议研究一种针对中风后 DED 的远程干预，该干预结合了 基于 iPad 的数字疗法称为 AKL-T01，可集中训练快速多任务处理技能，以及虚拟 元认知辅导。 AKL-T01 旨在针对中风后的常见机制 抑郁症状和执行功能障碍，这会减少大脑中内在的功能连接 执行控制网络（ECN）。虚拟元认知辅导旨在解决患者不了解的问题 加强将培训成果转化为日常运作的缺陷。在这项试点临床试验中，N=70 名患有以下疾病的患者 首次中风和干眼症将被随机分配接受干预，或接受一般控制条件 以及非针对性的认知刺激和元认知辅导。参与者将完成 在基线、第 3 周（治疗中期）时测量执行功能障碍、抑郁症状和残疾， 和第 6 周（结束治疗）。参与者将在基线和第 6 周完成静息态 fMRI 扫描。线性 混合效应模型将检验干预措施与更大的相关性的假设 与对照组相比，执行功能、抑郁症状和残疾有所改善。还 检验的是干预组内在功能连接性会有更大变化的假设 相对于对照组，从基线到第 6 周的 ECN 中。该项目有潜力解决 可扩展的方式，中风的一种高度衰弱的后果。它将生成可用于优化的数据 治疗效果，进一步细化和个性化干预，并进一步验证治疗目标。