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Completed

NCT Number: NCT02761330

Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia

This study is geared toward characterizing the recovery of brain activity and cognitive function following treatments of electroconvulsive therapy and ketamine general anesthesia.

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Key information

Conditions

Depression Behavior Behavioral Symptoms Cognition Disorders Cognitive Disorders Cognitive Dysfunction Confusion Delirium Mental Disorders Nervous System Diseases Neurobehavioral Manifestations Neurocognitive Disorders Neurologic Manifestations Pathological Conditions, Signs and Symptoms Seizures Signs and Symptoms

Age range

18 year–60 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Electroconvulsive therapy

Procedure

Dose of the ECT charge will be determined during titration session prior to randomization.

Other names: ECT

Primary outcomes

  1. 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.

  2. 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.

Secondary outcomes

  1. 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.

  2. 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:

    • wish to live (0 Moderate to Strong, 1 Weak, 2 None)
    • 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.

  3. ECT Seizure Duration

    Time frame: up to days 1-6

    Duration (in seconds) of seizure induced by ECT treatment

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

  • James S McDonnell Foundation

Registry information

Official study title

Cognitive Recovery After Electroconvulsive Therapy and General Anesthesia Reconstitution of Consciousness and Cognition (Phase 2)

Acronym: RCC2

Important dates

Study start
2016
Primary completion
2019
Study completion
2019
First posted
May 4, 2016
Registry last updated
Jun 28, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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