Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) Trial

异丙酚慢波诱导消除抑郁 (SWIPED) 试验

• 批准号: 10356683
• 负责人: Eric J Lenze
• 金额: $ 70.32万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-02-01 至 2026-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10356683
• 关键词: Accounting; Address; Adverse event; Aftercare; Age; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anesthetics; Antidepressive Agents; Autonomic nervous system; Biological Markers; Clinical Trials; Cognition; Cognitive; Dementia; Depressed mood; Disease; Dose; Double-Blind Method; Elderly; Electrodes; Enrollment; Evaluation; Excess Mortality; Frequencies; Functional disorder; Future; Goals; Grant; Home; Homeostasis; Hour; Impaired cognition; Individual; Infusion procedures; Intervention; Liquid substance; Measures; Mental Depression; Modeling; Moods; Outcome; Participant; Pathway interactions; Patients; Pattern; Pharmacology; Phase; Physiological; Population; Populations at Risk; Propofol; Public Health; Quality of life; Randomized; Reaction Time; Recurrence; Research Domain Criteria; Risk; Sedation procedure; Serious Adverse Event; Severities; Sleep; Sleep Deprivation; Sleep disturbances; Slow-Wave Sleep; Structure; Synaptic plasticity; Testing; Titrations; Unconscious State; United States National Institutes of Health; Work; aging population; alertness; arm; behavioral construct; cognitive function; depressive symptoms; design; disability; executive function; glymphatic system; improved; innovation; new therapeutic target; novel; novel strategies; novel therapeutics; precision medicine; primary endpoint; primary outcome; recruit; restoration; secondary outcome; sex; sleep pattern; statistics; suicide mortality; therapeutic target; treatment-resistant depression; vigilance; wearable device

ABSTRACT Treatment Resistant Depression (TRD) in older adults is a leading cause of disability, excess mortality from suicide, and dementia. Cognitive problems and sleep disturbances are common, contributing to recurrence and poor long-term outcomes. Disrupted slow wave sleep is at the nexus of depression and cognitive dysfunction in older adults. Novel approaches to target this core pathophysiology are lacking. Our mechanistic project, Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) Trial, is designed to elucidate the relationships between TRD, sleep disturbances, and cognitive impairments in older adults. Through personalized infusions targeting electroencephalographic (EEG) patterns, we aim for a systematic characterization of the relationships between the propofol-induced EEG slow waves, enhancement of slow wave sleep, and cognitive outcomes. Through the repurposing of propofol, this innovative proposal will establish whether EEG slow waves are a viable therapeutic target for novel antidepressant approaches. The project consists of two clinical trials (Phase 1 and Phase 2) in older adults with TRD. In Phase 1 we will enroll 15 individuals to receive a dose-finding propofol infusion, and then a second infusion at the dose determined to induce slow waves. This phase will establish that propofol both induces slow waves during the infusion and enhances slow wave sleep (SWS) on nights of sleep post-infusion. Then, in Phase 2 we will randomize 60 individuals to multiple infusions of propofol at either a dose that induces slow waves, or a subthreshold dose that does not induce slow waves, and we will examine short and long-term changes in post-infusion SWS as well as executive function, alertness, and depressive symptoms. This phase will test whether enhancement of SWS leads to improvements in cognitive function and mood. This work will enhance our understanding of core deficits contributing to poor mood and cognition in a population at risk for Alzheimer's disease and related dementias. With the rise in the aging population, we hope to provide translatable biomarkers and approaches for future precision medicine, with a long-term goal of improving public health and quality of life for those afflicted with TRD.

抽象的 老年人的难治性抑郁症 (TRD) 是造成残疾和死亡率过高的主要原因 自杀和痴呆症。认知问题和睡眠障碍很常见，导致复发和复发 长期结果不佳。慢波睡眠中断是抑郁症和认知功能障碍的关联因素 老年人。目前缺乏针对这一核心病理生理学的新方法。我们的机械项目， 丙泊酚慢波诱导消除抑郁 (SWIPED) 试验旨在阐明 老年人 TRD、睡眠障碍和认知障碍之间的关系。通过个性化 针对脑电图（EEG）模式的输注，我们的目标是系统地表征 异丙酚诱导的脑电图慢波、慢波睡眠增强和认知之间的关系 结果。通过重新利用异丙酚，这一创新提案将确定脑电图慢波是否 是新型抗抑郁方法的可行治疗靶点。该项目包括两项临床试验 （第一阶段和第二阶段）患有 TRD 的老年人。在第一阶段，我们将招募 15 人接受剂量探索 输注异丙酚，然后按确定诱发慢波的剂量进行第二次输注。这一阶段将 确定异丙酚在输注过程中诱导慢波并增强慢波睡眠（SWS） 输注后的夜间睡眠。然后，在第 2 阶段，我们将随机分配 60 名个体进行多次异丙酚输注 在诱发慢波的剂量或不诱发慢波的阈下剂量，我们将 检查输注后 SWS 的短期和长期变化以及执行功能、警觉性和 抑郁症状。此阶段将测试 SWS 的增强是否会导致认知能力的改善 功能和心情。这项工作将加深我们对导致不良情绪和不良情绪的核心缺陷的理解。 有阿尔茨海默病和相关痴呆症风险的人群的认知能力。随着老龄化的加剧 人口，我们希望为未来的精准医疗提供可翻译的生物标志物和方法， 改善 TRD 患者的公共健康和生活质量的长期目标。