NCT04680910

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

Precision Targeting of Propofol-induced Electroencephalographic Slow Waves: a Novel Phase I Paradigm for Treatment-resistant Major Depressive Disorder

• Status: Active Not Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 15 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 60 Years
• Healthy volunteers: Not accepted

Summary

Our hypothesis is that targeted propofol infusion in treatment-resistant depressed patients will induce slow wave activity during sedation and augment subsequent sleep slow wave activity. We will recruit 15 participants for this open label single arm Phase I trial. All participants will undergo two propofol infusions 2-6 days apart, with each infusion maximizing expression of EEG slow waves. To minimize bias, there will be no specific gender or ethnic background consideration for enrollment. This will be a single site investigation at Washington University Medical Center.

Detailed description

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 is designed to elucidate the relationships between TRD and sleep disturbances 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 and enhancement of slow wave sleep. Through the repurposing of propofol as a therapeutic probe, this innovative proposal will establish whether EEG slow waves are a viable therapeutic target for novel antidepressant approaches. Study Intervention Propofol will be infused through a peripheral IV, with the assistance of target-controlled infusion software and pumps, with an anticipated infusion duration of 1-2 hours. Concurrent high-density EEG will be acquired, but with an updated recording rig and sensor nets that use either Elefix conductive gel or salt solution. An Axis P3364LV network camera, synchronized to EEG recordings, will provide video for post-hoc analysis. Participants will be discharged home after nurse monitoring and fulfillment of post-anesthetic care unit criteria. Patients will be instructed by staff on operation of the Dreem headband for at-home overnight sleep EEG recordings. Patients will demonstrate ability to successfully wear the Dreem and initiate recordings without assistance. The device, charger, instruction sheet, and a link to a 2-minute instructional video will be provided to patients. This paradigm has been successful in the acquisition of preoperative sleep recordings in over 150 geriatric cardiac surgical patients and eight patients who underwent ECT for TRD (ClinicalTrials.gov NCT04451135). Dreem recordings will be obtained prior to the first propofol infusion and on evenings of propofol infusions. Additionally, recordings will be obtained for up to 6 nights within a 2-week period after the final infusion, to evaluate persistence of restoration of sleep architecture. Participants will exchange the device with staff during each in-person visit, to allow device examination and data download. Planned subgroup analyses include stratification by sex and age. For the purposes of Phase II of the study, additional subgroup analyses will be performed based on baseline sleep structure (e.g. total sleep time and proportion of time in N3 sleep), and time interval separating the two infusions.

Conditions

• Treatment-resistant Depression

Interventions

Type	Name	Description
DRUG	Propofol	Targeted propofol infusion in TRD patients will induce sedation with maximal expression of EEG slow waves and minimal burst suppression.
DIAGNOSTIC_TEST	Electroencephalography (EEG)	EEG will be recorded during propofol infusion and during overnight sleep. Sleep EEG data will be acquired for a minimum of one night prior to the first sedation session, providing a baseline measure. Additional overnight sleep recordings will be performed on day of sedation and subsequent nights.
DIAGNOSTIC_TEST	Slow-Wave Activity	Duration of slow waves during sedation will be evaluated using automated approaches. SWA during sedation will be calculated as the total power in the 0.5-4 Hz frequency band/total time in minutes. SWA during N2/N3 sleep will be calculated as the total power in the 0.5-4 Hz frequency band/total time in minutes in the N2 and N3 sleep stages. Delta sleep ratio will be computed from the SWA measured during the first and second N2/N3 cycles.

Timeline

• Start date: 2021-01-14
• Primary completion: 2024-07-01
• Completion: 2025-07-01
• First posted: 2020-12-23
• Last updated: 2024-12-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study
• FDA-regulated device study