Treatment-resistant DepressionPhase 1NCT04680910
Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) I
A Phase 1 study testing Propofol, Electroencephalography (EEG) and Slow-Wave Activity in people with Treatment-resistant Depression, run by Washington University School of Medicine at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Treatment-resistant Depression
- What is being tested?
- Propofol, Electroencephalography (EEG) and Slow-Wave Activity
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2021to 21 Sep 2025
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine/Barnes-Jewish Hospital
St Louis, Missouri, 63110
About this study
Official title: Precision Targeting of Propofol-induced Electroencephalographic Slow Waves: a Novel Phase I Paradigm for Treatment-resistant Major Depressive Disorder
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.
Read the 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
- Being tested
- Propofol, Electroencephalography (EEG), Slow-Wave Activity
- Medical subject headings
- Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PropofolDrug
Also called anesthetic
Targeted propofol infusion in TRD patients will induce sedation with maximal expression of EEG slow waves and minimal burst suppression.
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.
Slow-Wave ActivityDiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Propofol infusion | Experimental | Serial propofol infusions to maximally and safely induce unconsciousness and EEG slow waves while minimizing burst suppression. Receives: Drug: Propofol; Diagnostic Test: Electroencephalography (EEG); Diagnostic Test: Slow-Wave Activity |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 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.
Measured: 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.
Measured: Over three-week period of pre- and post-infusion sleep recordings
Secondary outcomes (6)
Effects on Suicidality
Evaluate whether propofol infusions are associated with suicidality. Suicidality assessed using Columbia Suicide Severity Rating Scale (C-SSRS). The scale for the CSSR-S is as follows: 0-No or Low Risk: No suicidal ideation or behaviors reported, 1-Moderate Risk: Suicidal thoughts with some intent or planning but no action taken, 2-High Risk: Suicidal ideation with intent, plan, or recent suicidal behaviors.
C-SSRS was administered approximately 1 week before the first infusion (baseline), and then approximately 1, 3, and 10 weeks after the second infusion.
No C-SSRS was obtained during the 2-6 days separating the first and second infusions.
Measured: 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)
Baseline measures are averages taken from 2-3 recordings before infusions. Averages for post-infusion are taken for measures derived on recordings on the evenings of morning propofol infusions.
Reported difference is calculated from averages of measures from post-infusion recordings and averages of baseline recordings.
Measured: 1 week before 1st infusion and recordings taken on both infusion nights
Change in Delta Sleep Ratio (Infusion Nights - Baseline)
Delta sleep ratio (DSR, calculated as the SWA of the 1st NREM cycle divided by the SWA of the 2nd NREM cycle, is unitless).
Baseline measures are averages taken from 2-3 recordings during the week before infusions.
Averages for infusion nights are taken for measures derived on recordings taken on the evenings of morning propofol infusions.
Reported change is the difference (average of infusion nights - baseline average)
Measured: 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
Calculated as total duration in N3/total sleep time and total duration in REM/total sleep time.
Baseline measures are averages of taken from 2-3 sleep recordings before infusions.
Post-infusion average is averaged from sleep recordings taken on the evenings of morning propofol infusions Reported change is infusion nights average - baseline average.
Measured: Baseline pre-infusion and nights of infusions
Evaluate Changes in Cognitive Function (MoCA) Between Pre-infusion Baseline and 3-weeks Post Infusion
Evaluate changes in cognitive function Change in Cognitive Performance on the Montreal Cognitive Assessment (MoCA). Total score of the MoCA is from 0-30, Normal: 26-30, Mild Cognitive Impairment (MCI): 18-25, Moderate Cognitive Impairment: 10-17, Severe Cognitive Impairment: <10 Examine potential positive or negative changes in cognition that may be associated with propofol infusion.
Reported change is post-infusion - baseline. Positive change indicated improvement. Negative change indicates worsening of cognition.
Measured: Two time points: baseline measure (approximately 1 week before the first infusion) and 3-weeks after second infusion
Number of Participants Able to Provide Complete Cognitive Assessment (Fluid Cognition) Using NIH Toolbox
Evaluate the feasibility in evaluating changes in cognitive function using NIH toolbox
Measured: pre-infusion baseline and approximately 3-weeks after the 2nd infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Dec 2020
- Study start14 Jan 2021
- Primary completion1 Jul 2024
- Study completion21 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Treatment-resistant DepressionStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Pilot Study for safety and feasibility (open label)
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Ben J.A. Palanca, Washington University School of Medicine
- Investigators
- Ben Palanca, MD PhD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04680910
- Sponsor's protocol ID
- 202008037
- Other IDs
- U01MH128483
- Status last verified
- Apr 2026
- First submitted
- 17 Dec 2020
- Last updated
- 23 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: Study protocol will be released in manuscript form. Outcome data will be uploaded to the NIMH Data Archive on a rolling basis. EEG data will be shared via the National Sleep Research Resource within three years of study completion.
Publications
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.
PubMed 26055669Duncan 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.
PubMed 22676966Doghramji 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.
PubMed 27514301Rios 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.
PubMed 38816055Rios 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.
PubMed 37105885