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Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia (RCC2)

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ClinicalTrials.gov Identifier: NCT02761330
Recruitment Status : Completed
First Posted : May 4, 2016
Results First Posted : June 28, 2021
Last Update Posted : June 28, 2021
Sponsor:
Collaborator:
James S McDonnell Foundation
Information provided by (Responsible Party):
Ben Palanca, Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE April 30, 2016
First Posted Date  ICMJE May 4, 2016
Results First Submitted Date  ICMJE September 11, 2020
Results First Posted Date  ICMJE June 28, 2021
Last Update Posted Date June 28, 2021
Actual Study Start Date  ICMJE April 2016
Actual Primary Completion Date September 11, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2021)
  • Change in Cognitive Function During Recovery: Rate of Recovery [ Time Frame: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. ]
    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:
    • Psychomotor Vigilance Task (PVT)
    • Digital Symbol Substitution Task (DSST)
    • Motor Praxis Task (MP)
    • Visual Object Learning Task (VOLT)
    • Abstract Matching (AM)
    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.
  • Change in Cognitive Function During Recovery: Initial Decrement [ Time Frame: 0, 30, 60, 90, 120 minutes following return of consciousness, assessed on treatment days 1-6. ]
    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:
    • Psychomotor Vigilance Task (PVT)
    • Digital Symbol Substitution Task (DSST)
    • Motor Praxis Task (MP)
    • Visual Object Learning Task (VOLT)
    • Abstract Matching (AM)
    Initial Decrement for this measure is defined as the difference between response times (in seconds) at baseline and t=0 for each task.
Original Primary Outcome Measures  ICMJE
 (submitted: May 3, 2016)
Change in cognitive function during recovery [ Time Frame: 0, 30, 60, 90, 120, 150, and 180 minutes following return of consciousness, assessed on treatment days 1-6. ]
Cognition Test Battery
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 25, 2021)
  • Delirium Incidence and Severity [ Time Frame: Immediately following return of consciousness (t=0) during treatment days 1-6. ]
    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.
  • Suicidality [ Time Frame: assessed at baseline on treatment days 1-6. ]
    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:
    1. wish to live (0 Moderate to Strong, 1 Weak, 2 None)
    2. wish to die (0 None, 1 Weak, 2 Moderate to Strong)
    The total scores range from 0-4. Lower scores indicate high suicide ideation, and high scores indicate low suicide ideation.
  • ECT Seizure Duration [ Time Frame: up to days 1-6 ]
    Duration (in seconds) of seizure induced by ECT treatment
  • ECT Electrical Dose [ Time Frame: First ECT treatment session during Treatment Week 1 ]
    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.
  • Subjective Assessment of Whether ECT Was Performed, Determined by Asking the Patient. [ Time Frame: Assessed at 120 minutes after return of responsiveness on treatment days 1-6 ]
    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.
  • Change in Mood Assessed Using the Mood Self-Assessment Manikin [ Time Frame: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 ]
    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.
  • Average Change in Mood Based on the Depression PROMIS-CAT [ Time Frame: baseline and 120 minutes after return of responsiveness, assessed on treatment days 1-6 ]
    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.
  • Change in Delta Band (0.5-4 Hz) Relative Power in the Scale EEG During Recovery [ Time Frame: baseline, post-ECT from 0-120 minutes ]
    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.
  • Change in Theta Band (4-8 Hz) Relative Power in the Scalp EEG During Recovery [ Time Frame: baseline, post-ECT from 0-120 minutes ]
    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.
  • Change in Alpha Band (8-13 Hz) Power in the Scalp EEG During Recovery [ Time Frame: baseline, post-ECT from 0-120 minutes ]
    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.
  • Change in Beta Band (13-20 Hz) Relative Power in the Scalp EEG During Recovery [ Time Frame: baseline, post-ECT from 0-120 minutes ]
    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.
  • Change in Anterior-Posterior Functional Connectivity in the Scalp During Recovery [ Time Frame: baseline, post-ECT from 0-120 minutes ]
    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.
  • Change in Anterior-Posterior Phase-lag in the Scalp EEG During Recovery [ Time Frame: baseline, post-ECT from 0 -120 minutes ]
    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.
  • Change in EEG Entropy in the Scalp EEG During Recovery [ Time Frame: baseline, Post-ECT from 0 -120 minutes ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 3, 2016)
  • Change in delta band (0.5-4 Hz) power in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in theta band (4-8 Hz) power in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in alpha band (8-13 Hz) power in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in beta band (13-30 Hz) power in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in anterior-posterior functional connectivity in the scalp during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in anterior-posterior phase-lag in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Change in EEG entropy in the scalp EEG during recovery [ Time Frame: baseline, post-ECT from 0-180 minutes during treatments days 1-6 ]
    EEG from 5 minute epochs of eyes open and eyes closed, during behavioral tasks, and during quiet resting
  • Delirium Incidence and Severity [ Time Frame: 0, 60, 120, 180 minutes after return of consciousness during treatment days 1-6. ]
    Assessed using 3D Confusion Assessment Method (CAM)
  • Suicidality [ Time Frame: assessed on treatment days 1-6 ]
    Scale of Suicidal Ideation
  • ECT Seizure duration [ Time Frame: up to days 1-6 ]
  • ECT Electrical dose [ Time Frame: up to 1 day ]
    The dose for each patient will have been determined on a dose-charge titration session prior to randomization and session 1.
  • Subjective assessment of whether ECT was performed, determined by asking the patient. [ Time Frame: Assessed at 180 minutes after return of responsiveness on treatment days 1-6 ]
    To assess patient blinding of treatment performed, the patient will be asked: "Based on how you feel, did you have ECT today?"
  • Change in mood assessed using the Mood Self-Assessment Manikin [ Time Frame: baseline and 180 minutes after return of responsiveness, assessed on treatment days 1-6 ]
    Mood Self-Assessment Manikin (SAM)
  • Change in Mood based on the depression PROMIS-CAT [ Time Frame: baseline and 180 minutes after return of responsiveness, assessed on treatment days 1-6 ]
    PROMIS-CAT (Patient Reported Outcomes Measurement Information System-Computer Adaptive Testing) for depression
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia
Official Title  ICMJE Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia Reconstitution of Consciousness and Cognition (Phase 2)
Brief Summary This study is geared toward characterizing the recovery of brain activity and cognitive function following treatments of electroconvulsive therapy and ketamine general anesthesia.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Primary Purpose: Basic Science
Condition  ICMJE
  • Depression
  • Delirium
  • Seizures
  • Cognitive Disorders
Intervention  ICMJE
  • Drug: 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.
  • Procedure: Electroconvulsive Therapy
    Dose of the ECT charge will be determined during titration session prior to randomization.
    Other Name: ECT
Study Arms  ICMJE
  • Active Comparator: 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.
    Intervention: Procedure: Electroconvulsive Therapy
  • Experimental: 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.
    Interventions:
    • Drug: Ketamine
    • Procedure: Electroconvulsive Therapy
  • Sham Comparator: 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.
    Intervention: Drug: Ketamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 17, 2018)
17
Original Estimated Enrollment  ICMJE
 (submitted: May 3, 2016)
20
Actual Study Completion Date  ICMJE September 11, 2019
Actual Primary Completion Date September 11, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Treatment resistant depression requiring outpatient ECT
  • Planned right unilateral ECT stimulation
  • English speaking
  • Able to provide written informed consent

Exclusion Criteria:

  • Known brain lesion or neurological illness that causes cognitive impairment
  • Schizophrenia
  • Schizoaffective disorder
  • Blindness or deafness or motor impediments that may impair performance for cognitive testing battery
  • Inadequate ECT seizure duration with etomidate
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02761330
Other Study ID Numbers  ICMJE 201512110
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Ben Palanca, Washington University School of Medicine
Study Sponsor  ICMJE Washington University School of Medicine
Collaborators  ICMJE James S McDonnell Foundation
Investigators  ICMJE Not Provided
PRS Account Washington University School of Medicine
Verification Date June 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP