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

NCT04680910 | Completed Phase 1 Results DMC FDA Drug FDA Device

• 2 other identifiers: 202008037U01MH128483
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Treatment-resistant Depression

Outcome Measures

Primary Outcomes (3)

• Number of Participants Without Serious Adverse Events During Propofol Infusions

  Adverse events and serious adverse events, including incidence, severity, and likelihood of relation to intervention. Evaluate whether serial propofol infusions are safe (\<5% serious adverse events directly attributable to infusions)

  Up to one week after propofol infusions

• Change in SWA During Propofol Infusions Compared to Awake Baseline Before Infusion

  Evaluate in geriatric TRD patients that propofol infusions can efficiently induce EEG slow waves during infusion. Sedation slow wave activity (SWA, frontal EEG power within 0.5-4 Hz frequency band) during propofol sedation compared to frontal EEG SWA during awake eyes closed baseline preceding infusion start. This is an indication of power/density of slow waves induced by propofol. Difference in 0.5-4Hz power (infusion - pre-infusion eyes closed). EEG power estimated using multitaper spectral analysis (Chronux toolbox). Difference values are averaged across the two infusions, leading to one outcome measure per participant.

  During two-hour propofol infusion

• Proportion of Infusion Completers With Augmentation of Sleep SWA After Propofol Infusion

  Evaluate Change in sleep slow wave activity during N2/N3 Sleep (post-infusion - pre-infusion). Pre-infusion measure of sleep slow wave activity is averaged across multiple recordings. Post-infusion measures are based on average of sleep slow activity from nights of morning propofol infusions. Evaluate whether propofol can augment total sleep SWA in greater or equal to 40% of study completers.

  Over three-week period of pre- and post-infusion sleep recordings

Secondary Outcomes (6)

• Effects on Suicidality

  Baseline, 1-week Post 2nd-Infusion, 3-week Post 2nd-Infusion, 10-week Post 2nd-Infusion

• Changes in N3 Duration, REM Duration, Total Sleep Time (Post-infusion Change Relative to Baseline)

  1 week before 1st infusion and recordings taken on both infusion nights

• Change in Delta Sleep Ratio (Infusion Nights - Baseline)

  One week before first infusion and on nights after morning infusions

• Changes in Proportion of Total Sleep Time in N3, Proportion of Total Sleep Time in REM

  Baseline pre-infusion and nights of infusions

• Evaluate Changes in Cognitive Function (MoCA) Between Pre-infusion Baseline and 3-weeks Post Infusion

  Two time points: baseline measure (approximately 1 week before the first infusion) and 3-weeks after second infusion

Other Outcomes (4)

• Number of Participants Able to Provide Sleep Diary Data on Circadian Rhythms

  Three-week period spanning pre- and post propofol infusions

• Anhedonia During Study Participation

  Baseline, 1-week Post Infusion, 3-week Post Infusion, and 10-weeks Post Infusion

• Depression Severity During the Study Period

  Baseline, 1-week after 2nd Infusion, 3-week after 2nd Infusion and 10-week after the 2nd infusion

Study Arms (1)

Propofol infusion

EXPERIMENTAL

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

Drug: Propofol; Diagnostic Test: Electroencephalography (EEG); Diagnostic Test: Slow-Wave Activity

Interventions

Propofol DRUG

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

Also known as: anesthetic

Propofol infusion

Electroencephalography (EEG) 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.

Propofol infusion

Slow-Wave Activity 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.

Propofol infusion

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Washington University School of Medicine: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Washington University School of Medicine/Barnes-Jewish Hospital

St Louis, Missouri, 63110, United States

Location

Related Publications (5)

• 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.

  PMID: 26055669 BACKGROUND

• 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.

  PMID: 22676966 BACKGROUND

• 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.

  PMID: 27514301 BACKGROUND

• 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.

  PMID: 38816055 BACKGROUND

• 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.

  PMID: 37105885 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Propofol; Anesthetics; Electroencephalography

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Central Nervous System Depressants; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses; Central Nervous System Agents; Therapeutic Uses; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Results Point of Contact

• Title: Dr. Ben Palanca
• Organization: Washington University School of Medicine

palancab@wustl.edu

314-273-9076

Study Officials

• Ben Palanca, MD PhD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: Pilot Study for safety and feasibility (open label)

Study Record Dates

• First Submitted: December 17, 2020
• First Posted: December 23, 2020
• Study Start: January 14, 2021
• Primary Completion: July 1, 2024
• Study Completion: September 21, 2025
• Last Updated: April 23, 2026
• Results First Posted: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Within three years of study completion.
• Access Criteria: Data use agreements may be required.

Locations

US (1)