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| Name | Class |
|---|---|
| James S McDonnell Foundation | OTHER |
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This study is geared toward characterizing the recovery of brain activity and cognitive function following treatments of electroconvulsive therapy and ketamine general anesthesia.
Seizures are often associated with loss of consciousness, possibly through effects on sub-cortical arousal systems, disruption of cortical-subcortical interactions, and ultimately through depressed neocortical function. Furthermore, people are often confused in the post-ictal state even when consciousness returns after a seizure. Disrupted cognitive function during the postictal phase has not been fully characterized but presents short and long-term implications. Many experience an acute disorder of attention, consciousness, and cognition, referred to as delirium. Memory deficits are also common. The neurobiology for these phenomena are incomplete and challenging to test, as seizures are typically sporadic and vary in intensity and character. In contrast, the setting of electroconvulsive therapy (ECT) provides the opportunity to study the reconstitution of consciousness and cognition following seizures in an elective and predictable context.
There is no standard agent used to induce general anesthesia during ECT. Ketamine is receiving greater attention as an infusion for treating depression and for its potential benefits on improving ECT efficacy and expediting cognitive recovery. Further data are needed to determine whether ketamine may improve recovery of cognitive function relative to etomidate, a commonly used anesthetic for general anesthesia during ECT.
The investigators will evaluate the cognition function and electroencephalographic patterns that accompany the recovery from ECT and general anesthesia. Twenty patients with refractory depression will be randomized in this interventional single-blinded randomized crossover trial. Each patient will complete seven study visits. The first visit will be conducted during the dose-charge titration ECT treatment with etomidate anesthesia. After this session, patients will be randomized to three sessions each week for two weeks (six treatments total). Over the first week patients will be randomized in order for three treatment arms: (1) etomidate general anesthesia and ECT, (2) ketamine general anesthesia and ECT, and (3) ketamine alone. Patients will be blinded to the treatment arm for each session. Baseline and post-treatment measurements of cognition and ECT will be acquired on each of the six treatment sessions.
Patients that agree will have a MRI.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Etomidate + ECT | Active Comparator | General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
|
| Ketamine + ECT | Experimental | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
|
| Ketamine alone | Sham Comparator | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Ketamine | Drug | Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Cognitive Function During Recovery: Rate of Recovery | A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery:
Rate of Recovery for this measure is defined as the time (in inverse hours) for participants to return to their baseline performance for each task. | 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. |
| Change in Cognitive Function During Recovery: Initial Decrement | A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery:
Initial Decrement for this measure is defined as the difference between response times (in seconds) at baseline and t=0 for each task. | 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. |
| Measure | Description | Time Frame |
|---|---|---|
| Delirium Incidence and Severity | Assessed using 3D Confusion Assessment Method (CAM). The groups/arms for this outcome are separated by anesthetic regimen; however, due to the crossover design of this study all participants are included in analyses for each group. | Immediately following return of consciousness (t=0) during treatment days 1-6. |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University School of Medicine | St Louis | Missouri | 63110 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33652270 | Derived | Hickman LB, Kafashan M, Labonte AK, Chan CW, Huels ER, Guay CS, Guan MJ, Ching S, Lenze EJ, Farber NB, Avidan MS, Hogan RE, Palanca BJA. Postictal generalized electroencephalographic suppression following electroconvulsive therapy: Temporal characteristics and impact of anesthetic regimen. Clin Neurophysiol. 2021 Apr;132(4):977-983. doi: 10.1016/j.clinph.2020.12.018. Epub 2021 Jan 28. | |
| 33137572 |
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14 of 17 participants were randomized. Of those not randomized, 1 participant's treatment course was canceled by clinical staff, 1 participant withdrew consent prior to any study participation, and 1 participant was deemed ineligible.
17 patients were enrolled for study participation between May 2016 and July 2018 at Barnes Jewish Hospital in St. Louis, MO.
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| ID | Title | Description |
|---|---|---|
| FG000 | Ketamine +ECT, Etomidate + ECT, Ketamine Sham | Participants first received ECT treatment under Ketamine general anesthesia, then ECT treatment under Etomidate anesthesia, and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| FG001 | Ketamine +ECT, Ketamine Sham, Etomidate + ECT | Participants first received ECT treatment under Ketamine general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| FG002 | Etomidate +ECT, Ketamine + ECT, Ketamine Sham | Participants first received ECT treatment under Etomidate general anesthesia, then ECT treatment under Ketamine general anesthesia and finally participants received Ketamine general anesthesia with sham ECT. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| FG003 | Etomidate +ECT, Ketamine Sham, Ketamine +ECT | Participants first received ECT treatment under Etomidate general anesthesia, then Ketamine general anesthesia with sham ECT and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| FG004 | Ketamine Sham, Etomidate +ECT, Ketamine +ECT | Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Etomidate general anesthesia and finally participants received ECT treatment under Ketamine anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| FG005 | Ketamine Sham, Ketamine +ECT, Etomidate +ECT | Participants first received Ketamine general anesthesia with sham ECT, then ECT treatment under Ketamine general anesthesia and finally participants received ECT treatment under Etomidate anesthesia. Ketamine+ECT: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine Sham: General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Etomidate + ECT: General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Treatment Week 1 |
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| ||||||||||||||||||
| Treatment Week 2 |
|
Per the participant flow report, 17 patients were enrolled in study procedures. Only 10 completed the study, per the full protocol, as reported. However, data from 15 participants are eligible for analyses. So, all analyses were done with 15 participants.
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| ID | Title | Description |
|---|---|---|
| BG000 | AllParticipants | All participants enrolled in study procedures. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change in Cognitive Function During Recovery: Rate of Recovery | A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery:
Rate of Recovery for this measure is defined as the time (in inverse hours) for participants to return to their baseline performance for each task. | Participants with cogntive task data complete for the majority of timepoints following return of responsiveness for more than one treatment day were included in analyses. Additional participants were excluded for individual cognitive task measures for being extreme outliers. | Posted | Median | Inter-Quartile Range | inverse hours | 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. |
|
approximately 3 weeks
Each group/arm of this crossover study were reported separately. All participants who completed at least 1 treatment session were included in adverse event reporting.
Each group contains a total of 15 participants, as each participant completed each arm of the study at least once.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ketamine +ECT | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Alyssa Labonte | Washington Universtiy School of Medicine | 314-273-7338 | alabonte@wustl.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Feb 25, 2019 | Sep 1, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D003863 | Depression |
| D003693 | Delirium |
| D012640 | Seizures |
| D060825 | Cognitive Dysfunction |
| D003221 | Confusion |
| D001523 | Mental Disorders |
| D019954 | Neurobehavioral Manifestations |
| D012816 | Signs and Symptoms |
| D009461 | Neurologic Manifestations |
| ID | Term |
|---|---|
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
| D009422 | Nervous System Diseases |
| D013568 | Pathological Conditions, Signs and Symptoms |
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| ID | Term |
|---|---|
| D007649 | Ketamine |
| D004565 | Electroconvulsive Therapy |
| ID | Term |
|---|---|
| D003510 | Cyclohexanes |
| D003516 | Cycloparaffins |
| D006840 | Hydrocarbons, Alicyclic |
| D006844 | Hydrocarbons, Cyclic |
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| Electroconvulsive Therapy | Procedure | Dose of the ECT charge will be determined during titration session prior to randomization. |
|
|
| Suicidality | The groups/arms for this outcome are combined as a whole-group analysis due to the crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. All participants included in analyses completed all treatments, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in suicidality from baseline to treatment 6 based on the Scale of Suicide Ideation. The measure completed was the Scale of Suicide Ideation. For this study, participants completed the following questions of the questionnaire:
The total scores range from 0-4. Lower scores indicate high suicide ideation, and high scores indicate low suicide ideation. | assessed at baseline on treatment days 1-6. |
| ECT Seizure Duration | Duration (in seconds) of seizure induced by ECT treatment | up to days 1-6 |
| ECT Electrical Dose | The electrical dose necessary for seizure induction is determined during a dose-charge titration session prior to participant randomization and session 1. These results report the average electrical dose across all participants for the first treatment session during Treatment Week 1. The range for these data is 0 - 100% electrical charge. | First ECT treatment session during Treatment Week 1 |
| Subjective Assessment of Whether ECT Was Performed, Determined by Asking the Patient. | To assess patient blinding of treatment performed, the patient will be asked: "Based on how you feel, did you have ECT today?" Results indicate participants correctly answering the subjective assessment. | Assessed at 120 minutes after return of responsiveness on treatment days 1-6 |
| Change in Mood Assessed Using the Mood Self-Assessment Manikin | Mood Self-Assessment Manikin (SAM) Scale: 1 (very unpleasant) - 9 (very pleasant). The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the SAM. Additionally, data collected at baseline are not dependent on the study group/arm. | baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 |
| Average Change in Mood Based on the Depression PROMIS-CAT | PROMIS-CAT (Patient Reported Outcomes Measurement Information System-Computer Adaptive Testing) for depression The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the PROMIS-CAT. Additionally, data collected at baseline are not dependent on the study group/arm. | baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 |
| Change in Delta Band (0.5-4 Hz) Relative Power in the Scale EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the delta band over the sum of total power between 0.5 - 70Hz. | baseline, post-ECT from 0-120 minutes |
| Change in Theta Band (4-8 Hz) Relative Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the theta band over the sum of total power between 0.5 - 70Hz. | baseline, post-ECT from 0-120 minutes |
| Change in Alpha Band (8-13 Hz) Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the alpha band over the sum of total power between 0.5 - 70Hz. | baseline, post-ECT from 0-120 minutes |
| Change in Beta Band (13-20 Hz) Relative Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the beta band over the sum of total power between 0.5 - 70Hz. | baseline, post-ECT from 0-120 minutes |
| Change in Anterior-Posterior Functional Connectivity in the Scalp During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the coherence measure, which is used for tracking changes in anterior-posterior functional connectivity. Coherence is a measure of synchronization between two signals which is used to measure anterior-posterior functional connectivity. Coherence is a unitless measure between 0 and 1. High coherence between time-series of two neural populations reflects higher efficiency in communication between those populations and therefore stronger functional connectivity. | baseline, post-ECT from 0-120 minutes |
| Change in Anterior-Posterior Phase-lag in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Phase-lag was assessed using the Phase-Lag Index (PLI), a measure ranging from 0 - 1. A consistent phase-lag between two tim-series results in a PLI of 1. A time-series without coupling results in a PLI near or equaling 0. Results show the difference in anterior-posterior PLI between baseline and post-ECT. | baseline, post-ECT from 0 -120 minutes |
| Change in EEG Entropy in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as permutation entropy (PE) measures in posterior regions, which we are using to track changes in scalp EEG entropy. Permutation Entropy (PE) is a measure that is used to quantify the complexity of time series signals. It is a unitless measure between 0 and 1. Lower the PE represents a more regular and more deterministic time series while higher PE represents a more complex time series. | baseline, Post-ECT from 0 -120 minutes |
| Derived |
| Hickman LB, Hogan RE, Labonte AK, Kafashan M, Chan CW, Huels ER, Ching S, Lenze EJ, Maccotta L, Eisenman LN, Keith Day B, Farber NB, Avidan MS, Palanca BJA. Voltage-based automated detection of postictal generalized electroencephalographic suppression: Algorithm development and validation. Clin Neurophysiol. 2020 Dec;131(12):2817-2825. doi: 10.1016/j.clinph.2020.08.015. Epub 2020 Sep 11. |
| 29867602 | Derived | Palanca BJA, Maybrier HR, Mickle AM, Farber NB, Hogan RE, Trammel ER, Spencer JW, Bohnenkamp DD, Wildes TS, Ching S, Lenze E, Basner M, Kelz MB, Avidan MS. Cognitive and Neurophysiological Recovery Following Electroconvulsive Therapy: A Study Protocol. Front Psychiatry. 2018 May 14;9:171. doi: 10.3389/fpsyt.2018.00171. eCollection 2018. |
| COMPLETED |
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| NOT COMPLETED |
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| years |
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| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| OG000 |
| Etomidate + ECT |
General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization. |
| OG001 | Ketamine + ECT | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. Electroconvulsive Therapy: Dose of the ECT charge will be determined during titration session prior to randomization. |
| OG002 | Ketamine Alone | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. Ketamine: Ketamine will be used to induce general anesthesia with or without subsequent ECT. Within a single patient, the dose will remain consistent throughout the study and is estimated to be 2 mg/kg. |
|
|
|
| Primary | Change in Cognitive Function During Recovery: Initial Decrement | A cognitive test battery was administered at 0, 30, 60, 90, and 120 minutes following return of consciousness after general anesthesia on each treatment day (1-6). The data from each treatment day (1-6) were averaged for analyses. Cognition Test Battery:
Initial Decrement for this measure is defined as the difference between response times (in seconds) at baseline and t=0 for each task. | Participants with cogntive task data complete for the majority of timepoints following return of responsiveness for more than one treatment day were included in analyses. Additional participants were excluded for individual cognitive task measures for being extreme outliers. | Posted | Median | Inter-Quartile Range | seconds | 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. |
|
|
|
|
| Secondary | Delirium Incidence and Severity | Assessed using 3D Confusion Assessment Method (CAM). The groups/arms for this outcome are separated by anesthetic regimen; however, due to the crossover design of this study all participants are included in analyses for each group. | All participants (12) who completed both baseline and t=0 delirium assessments on at least one treatment day. | Posted | Number | Delirium Assessments | Immediately following return of consciousness (t=0) during treatment days 1-6. | Delirium Assessments | Delirium Assessments |
|
|
|
| Secondary | Suicidality | The groups/arms for this outcome are combined as a whole-group analysis due to the crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. All participants included in analyses completed all treatments, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in suicidality from baseline to treatment 6 based on the Scale of Suicide Ideation. The measure completed was the Scale of Suicide Ideation. For this study, participants completed the following questions of the questionnaire:
The total scores range from 0-4. Lower scores indicate high suicide ideation, and high scores indicate low suicide ideation. | 114 Assessments of suicidality were completed across 13 participants on days 1-6. Data reported show the average change in suicidality from baseline to treatment 6 based on the Scale of Suicide Ideation. | Posted | Mean | Standard Deviation | score on a scale | assessed at baseline on treatment days 1-6. | Suicide Assessments | Suicide Assessments |
|
|
|
| Secondary | ECT Seizure Duration | Duration (in seconds) of seizure induced by ECT treatment | These data were not collected from patient ECT procedure records and therefore were not analyzed. | Posted | up to days 1-6 |
|
|
| Secondary | ECT Electrical Dose | The electrical dose necessary for seizure induction is determined during a dose-charge titration session prior to participant randomization and session 1. These results report the average electrical dose across all participants for the first treatment session during Treatment Week 1. The range for these data is 0 - 100% electrical charge. | Results are shown for all 13 participants who completed at least one treatment session following the dose charge titration session. | Posted | Mean | Standard Deviation | percentage of electrical charge | First ECT treatment session during Treatment Week 1 |
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| Secondary | Subjective Assessment of Whether ECT Was Performed, Determined by Asking the Patient. | To assess patient blinding of treatment performed, the patient will be asked: "Based on how you feel, did you have ECT today?" Results indicate participants correctly answering the subjective assessment. | The sample analyzed for each group consists of the total number of treatments performed with paired subjective assessments out of 12 participants. | Posted | Count of Units | Subjective Assessments w/ paired Tx | Assessed at 120 minutes after return of responsiveness on treatment days 1-6 | Subjective Assessments w/ paired Tx | Subjective Assessments w/ paired Tx |
|
|
|
| Secondary | Change in Mood Assessed Using the Mood Self-Assessment Manikin | Mood Self-Assessment Manikin (SAM) Scale: 1 (very unpleasant) - 9 (very pleasant). The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the SAM. Additionally, data collected at baseline are not dependent on the study group/arm. | The average change in SAM score from baseline to t=120 for all sessions across all participants (t=120 - baseline). | Posted | Mean | Standard Deviation | score on a scale | baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 | SAM Assessments | SAM Assessments |
|
|
|
| Secondary | Average Change in Mood Based on the Depression PROMIS-CAT | PROMIS-CAT (Patient Reported Outcomes Measurement Information System-Computer Adaptive Testing) for depression The groups/arms for this outcome are combined as a whole-group analysis due to the Crossover design of this study, as pre-specified by the study protocol. Breaking up the analyses into the various arms of the study would change our scientific questions and approach. Further, any statistical analyses would be underpowered due to low participant numbers in each arm. Thus, the results are combined and reported as a whole group analysis. All participants included in analyses completed all treatments included in the study, the various arms for the study vary only in the order in which participants received each treatment. These data show the change in mood from baseline to treatment 6 based on the PROMIS-CAT. Additionally, data collected at baseline are not dependent on the study group/arm. | All 13 participants who completed the depression PROMS-CAT both before and after treatment (baseline and 120 minutes following return of responsiveness) on at least one treatment day. | Posted | Mean | Standard Deviation | score on a scale | baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 |
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| Secondary | Change in Delta Band (0.5-4 Hz) Relative Power in the Scale EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the delta band over the sum of total power between 0.5 - 70Hz. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | percent of total power | baseline, post-ECT from 0-120 minutes |
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|
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| Secondary | Change in Theta Band (4-8 Hz) Relative Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the theta band over the sum of total power between 0.5 - 70Hz. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | percent of total power | baseline, post-ECT from 0-120 minutes |
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| Secondary | Change in Alpha Band (8-13 Hz) Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the alpha band over the sum of total power between 0.5 - 70Hz. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | percent of total power | baseline, post-ECT from 0-120 minutes |
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| Secondary | Change in Beta Band (13-20 Hz) Relative Power in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the percent of total power in the beta band over the sum of total power between 0.5 - 70Hz. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | percent of total power | baseline, post-ECT from 0-120 minutes |
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| Secondary | Change in Anterior-Posterior Functional Connectivity in the Scalp During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as the coherence measure, which is used for tracking changes in anterior-posterior functional connectivity. Coherence is a measure of synchronization between two signals which is used to measure anterior-posterior functional connectivity. Coherence is a unitless measure between 0 and 1. High coherence between time-series of two neural populations reflects higher efficiency in communication between those populations and therefore stronger functional connectivity. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | unitless | baseline, post-ECT from 0-120 minutes |
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| Secondary | Change in Anterior-Posterior Phase-lag in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Phase-lag was assessed using the Phase-Lag Index (PLI), a measure ranging from 0 - 1. A consistent phase-lag between two tim-series results in a PLI of 1. A time-series without coupling results in a PLI near or equaling 0. Results show the difference in anterior-posterior PLI between baseline and post-ECT. | Posted | Median | Inter-Quartile Range | Phase Lag Index (PLI) | baseline, post-ECT from 0 -120 minutes |
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| Secondary | Change in EEG Entropy in the Scalp EEG During Recovery | High-density EEG collected during 5-minute epochs of eyes-closed quiet resting at baseline and post-ECT. Results are reported as permutation entropy (PE) measures in posterior regions, which we are using to track changes in scalp EEG entropy. Permutation Entropy (PE) is a measure that is used to quantify the complexity of time series signals. It is a unitless measure between 0 and 1. Lower the PE represents a more regular and more deterministic time series while higher PE represents a more complex time series. | Participants with EEG data collected at baseline at T0 post-ECT for at least 1 ECT session were included in analyses. | Posted | Median | Inter-Quartile Range | unitless | baseline, Post-ECT from 0 -120 minutes |
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| 0 |
| 15 |
| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | Etomidate +ECT | General anesthesia for ECT will be induced with etomidate, approximately 0.2 mg/kg (0.1-0.6 mg/kg). Following application of stimulation electrodes to the patients scalp, an ECT charge will be administered at the previously determined therapeutic dose. | 0 | 15 | 0 | 15 | 0 | 15 |
| EG002 | Ketamine Sham | General anesthesia for ECT will be induced with ketamine, approximately 2 mg/kg (1-2.5 mg/kg). Following application of stimulation electrodes to the patients scalp, no ECT charge will be administered. | 0 | 15 | 0 | 15 | 0 | 15 |
Not provided
Not provided
Not provided
| D019965 | Neurocognitive Disorders |
| D003072 | Cognition Disorders |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |
| D003295 | Convulsive Therapy |
| D013000 | Psychiatric Somatic Therapies |
| D004191 | Behavioral Disciplines and Activities |
| D004597 | Electroshock |
| D011580 | Psychological Techniques |
| DSST Initial Decrement |
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| MP Initial Decrement |
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| VOLT Initial Decrement |
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| AM Initial Decrement |
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Comparison between the Ketamine + ECT and Ketamine Alone groups for the recovery rate of Psychomotor Vigilance Task (PVT) reaction time.
| Wilcoxon Signed-Ranked Test |
| 0.039 |
Not adjusted for multiple comparisons. |
| Other |
| Comparison between the Etomidate + ECT and Ketamine + ECT groups for the initial decrement of Digital Symbol Substitution Task (DSST) reaction time. | Wilcoxon Signed-Ranked Test | 0.031 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Ketamine + ECT and Ketamine Alone groups for the initial decrement of Digital Symbol Substitution Task (DSST) reaction time. | Wilcoxon Signed-Ranked Test | 1.0 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Etomidate + ECT and Ketamine + ECT groups for the initial decrement of Motor Praxis task (MP) reaction time. | Wilcoxon Signed-Ranked Test | 0.195 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Ketamine + ECT and Ketamine Alone groups for the initial decrement of Motor Praxis task (MP) reaction time. | Wilcoxon Signed-Ranked Test | 0.570 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Etomidate + ECT and Ketamine + ECT groups for the initial decrement of Visual Object Learning Task (VOLT) reaction time. | Wilcoxon Signed-Ranked Test | 0.031 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Ketamine + ECT and Ketamine Alone groups for the initial decrement of Visual Object Learning Task (VOLT) reaction time. | Wilcoxon Signed-Ranked Test | 0.016 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Etomidate + ECT and Ketamine + ECT groups for the initial decrement of Abstract Matching (AM) task reaction time. | Wilcoxon Signed-Ranked Test | 1.00 | Not adjusted for multiple comparisons. | Other |
| Comparison between the Ketamine + ECT and Ketamine Alone groups for the initial decrement of Abstract Matching (AM) task reaction time. | Wilcoxon Signed-Ranked Test | 0.109 | Not adjusted for multiple comparisons. | Other |
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| Positive Delirium at t=0 |
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| Negative Delirium at t=0 |
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| Wilcoxon signed-rank paired test |
| 0.301 |
| Other |
| Comparison of relative power in the delta band at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.557 | Other |
| Wilcoxon signed-rank paired test |
| 0.734 |
| Other |
| Comparison of relative power in the theta band at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.322 | Other |
| Wilcoxon signed-rank paired test |
| 0.039 |
| Other |
| Comparison of relative power in the alpha band at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.375 | Other |
| Wilcoxon signed-rank paired test |
| 0.910 |
| Other |
| Comparison of relative power in the beta band at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.625 | Other |
| Wilcoxon signed-rank paired test |
| 0.910 |
| Other |
| Comparison of anterior-posterior functional connectivity (coherence) at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.625 | Other |
| Wilcoxon signed-rank paired test |
| 0.496 |
| Other |
| Comparison of anterior-posterior phase-lag (PLI) at baseline compared to T0 following return of responsiveness. | Wilcoxon signed-rank paired test | 0.160 | Other |
| Wilcoxon Signed-Ranked Test |
| 0.359 |
| Other |
| Comparison of EEG Entropy using Permutation Entropy (PE) measures at baseline compared to T0 following return of responsiveness. | Wilcoxon Signed-Ranked Test | 0.375 | Other |