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: 10559540
• 负责人: Eric J Lenze
• 金额: $ 70.69万
• 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/10559540
• 关键词: Accounting; Address; Adverse event; Aftercare; Age; Alzheimer' s disease related dementia; Alzheimer' s disease risk; Anesthetics; Antidepressive Agents; Autonomic nervous system; Behavior; Biological Markers; Clinical Trials; Cognition; Cognitive; Dementia; Depressed mood; Disease; Dose; Double-Blind Method; Dryness; Elderly; Electrodes; Electroencephalography; 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; 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; cognitive function; depressive symptoms; design; disability; executive function; glymphatic system; improved; innovation; new therapeutic target; novel; novel strategies; novel therapeutics; pharmacologic; 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 老年人的耐药抑郁症（TRD）是残疾的主要原因，过多的死亡率 自杀和痴呆症。认知问题和睡眠障碍很常见，导致复发和 长期不良结果。慢波睡眠中断是在抑郁症和认知功能障碍的联系 老年人。缺乏针对这种核心病理生理学的新方法。我们的机械项目， 丙泊酚慢波诱导以消除抑郁症（扫描）试验，旨在阐明 老年人的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 丙泊酚引起的脑电图慢波，慢波睡眠的增强与认知之间的关系 结果。通过对丙泊酚的重新利用，这项创新的提议将确定eeg是否慢波 是新型抗抑郁药的可行治疗靶标。该项目由两个临床试验组成 （第1阶段和第2阶段）在TRD的老年人中。在第1阶段，我们将招募15个人接受剂量调查 丙泊酚输注，然后在确定诱导慢波的剂量下进行第二次输注。这个阶段将 确定丙泊酚在输注过程中都诱导慢波，并增强慢波睡眠（SWS） 入口后睡眠。然后，在第2阶段，我们将随机将60个个体与多次输注丙泊酚 在诱导慢波的剂量或不引起慢波的亚阈值剂量的剂量上，我们将 检查灌注后SWS以及执行功能，警觉性和长期变化 抑郁症状。此阶段将测试SWS的增强是否会改善认知能力 功能和心情。这项工作将增强我们对核心缺陷的理解，导致情绪差， 患有阿尔茨海默氏病风险和相关痴呆症风险的人群的认知。随着衰老的增长 人口，我们希望提供可翻译的生物标志物和方法，以提供未来的精确医学， 改善患有TRD的人的公共健康和生活质量的长期目标。