Trial Outcomes & Findings for Slow Wave Induction by Propofol to Eliminate Depression (SWIPED) I (NCT NCT04680910)

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

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)

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.

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.

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.

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.

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)

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.

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.

Evaluate the feasibility in evaluating changes in cognitive function using NIH toolbox

Examine feasibility of acquiring propofol-associated changes on circadian rhythms using a sleep diary These measures are important for evaluating feasibility of collection in Phase II.

Examine the feasibility of acquiring propofol-associated changes on anhedonia Measure of anhedonia with the Snaith-Hamilton Pleasure Scale (SHAPS), scale: rated on a 4-point Likert scale: 0 = strongly disagree, 1 = disagree, 2 = agree, 3 = strongly agree, Scoring: Items marked with \* (questions 2, 4, 5, 7, 9) are reverse coded with answer choices as follows: definitely agree, agree, disagree, and strongly disagree. All other items are sum-scored. (total score ranges from 0-14). A higher score indicates greater anhedonia (lower pleasure), with scores \<=2 typically considered normal, while scores \>=3 indicate significant anhedonia.Total score is tabulated from summation of subscores, with a greater score indicating more anhedonia. Medians across the population are reported for each time point. These measures are important for evaluating the feasibility of collection in Phase II.

Examine feasibility of acquiring propofol-associated changes on depression symptoms Measure of Depressive Symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), total score ranges from 0-60, 0-6: No depression, 7-19: Mild depression, 20-34: Moderate depression, and 35-60: Severe depression. Baseline measures were taken within 1-week of the first propofol infusion. This assesses for changes in depression relative to the 2nd infusion of propofol. No assessments were taken during the 2-6 days between the first and second infusions. These measures are important for evaluating feasibility of collection in Phase II.

Examine the feasibility of acquiring propofol-associated changes on affect Measure of affect using the Feelings Scale, (-5 to 5) as follows: -5 = Very Bad, -3 = Bad, -1 = Fairly Bad, 0 = Neutral, 1 = Fairly Good, 3 = Good, 5 = Very Good This assesses any affect immediately after propofol infusions These measures are important for evaluating the feasibility of collection in Phase II. Assessments were taken before and after both infusions. Change is the post - pre-infusion score for an individual infusion. Greater change = higher affect. Changes for each individual were the average across both infusions. Median changes are reported across all participants.