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

NCT ID: NCT04680910

Last Updated: 2024-12-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-01-14

Study Completion Date

2025-07-01

Brief Summary

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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

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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

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Treatment-resistant Depression

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Pilot Study for safety and feasibility (open label)
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Propofol infusion

Serial propofol infusions to maximally and safely induce unconsciousness and EEG slow waves while minimizing burst suppression.

Group Type EXPERIMENTAL

Propofol

Intervention Type DRUG

Targeted propofol infusion in TRD patients will induce sedation with maximal expression of EEG slow waves and minimal burst suppression.

Electroencephalography (EEG)

Intervention Type DIAGNOSTIC_TEST

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.

Slow-Wave Activity

Intervention Type DIAGNOSTIC_TEST

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.

Interventions

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Propofol

Targeted propofol infusion in TRD patients will induce sedation with maximal expression of EEG slow waves and minimal burst suppression.

Intervention Type DRUG

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.

Intervention Type 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.

Intervention Type DIAGNOSTIC_TEST

Other Intervention Names

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anesthetic

Eligibility Criteria

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Inclusion Criteria

* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study
* Age 60 or greater
* English speaking (as an interpreter will not be readily available should a participant need to convey any safety concerns during the propofol infusion sessions or require guidance on conducting at-home sleep recordings)
* Treatment-resistant Depression (non-responsive to at least two adequate trials of oral antidepressants for current episode).

Exclusion Criteria

* Presence of symptomatic coronary artery disease
* Presence of marked congestive heart failure/cardiomyopathy (NYHA \> Class III, LVEF \<40%, greater than mild RV systolic dysfunction)
* Prior reaction to propofol
* Resting heart rate \< 50 bpm
* Treatment with Electroconvulsive therapy/Transcranial Magnetic Stimulation/vagal nerve stimulation within 6 weeks
* Body mass index \> 35
* C-SSRS of 4 or greater (active suicidal ideation with some intent and with/without a specific plan)
* MoCA score \< 23 (at least mild dementia)
* Non-prescribed used of amphetamines, opioids, marijuana, cocaine, or phencyclidine
* Intake of \> 14 beers/week (or equivalent)
* Anesthetic exposure in the past 4 weeks
* Concurrent use of benzodiazepines \> 2 mg/day lorazepam or equivalent, trazodone \> 50 mg/day, or gabapentin \> 600 mg/day.
Minimum Eligible Age

60 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Washington University School of Medicine

OTHER

Sponsor Role lead

Responsible Party

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Ben J.A. Palanca

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ben Palanca, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

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Washington University School of Medicine/Barnes-Jewish Hospital

St Louis, Missouri, United States

Site Status

Countries

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United States

References

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Murphy MJ, Peterson MJ. Sleep Disturbances in Depression. Sleep Med Clin. 2015 Mar;10(1):17-23. doi: 10.1016/j.jsmc.2014.11.009. Epub 2014 Dec 12.

Reference Type BACKGROUND
PMID: 26055669 (View on PubMed)

Duncan WC, Sarasso S, Ferrarelli F, Selter J, Riedner BA, Hejazi NS, Yuan P, Brutsche N, Manji HK, Tononi G, Zarate CA. Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol. 2013 Mar;16(2):301-11. doi: 10.1017/S1461145712000545. Epub 2012 Jun 7.

Reference Type BACKGROUND
PMID: 22676966 (View on PubMed)

Doghramji K, Jangro WC. Adverse Effects of Psychotropic Medications on Sleep. Psychiatr Clin North Am. 2016 Sep;39(3):487-502. doi: 10.1016/j.psc.2016.04.009. Epub 2016 Jun 24.

Reference Type BACKGROUND
PMID: 27514301 (View on PubMed)

Rios RL, Green M, Smith SK, Kafashan M, Ching S, Farber NB, Lin N, Lucey BP, Reynolds CF, Lenze EJ, Palanca BJA; SWIPED Study Team. Propofol enhancement of slow wave sleep to target the nexus of geriatric depression and cognitive dysfunction: protocol for a phase I open label trial. BMJ Open. 2024 May 30;14(5):e087516. doi: 10.1136/bmjopen-2024-087516.

Reference Type DERIVED
PMID: 38816055 (View on PubMed)

Rios RL, Kafashan M, Hyche O, Lenard E, Lucey BP, Lenze EJ, Palanca BJA. Targeting Slow Wave Sleep Deficiency in Late-Life Depression: A Case Series With Propofol. Am J Geriatr Psychiatry. 2023 Aug;31(8):643-652. doi: 10.1016/j.jagp.2023.03.009. Epub 2023 Mar 28.

Reference Type DERIVED
PMID: 37105885 (View on PubMed)

Other Identifiers

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U01MH128483

Identifier Type: NIH

Identifier Source: secondary_id

View Link

202008037

Identifier Type: -

Identifier Source: org_study_id