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.

摘要