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Ketamine Anesthesia for Improvement of Depression in ECT (KAID)

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ClinicalTrials.gov Identifier: NCT02752724
Recruitment Status : Completed
First Posted : April 27, 2016
Last Update Posted : June 5, 2018
Sponsor:
Information provided by (Responsible Party):
Dr. Charles William Carspecken, MD, MBA, MSc, VA Puget Sound Health Care System

Brief Summary:

The purpose of this prospective randomized clinical trial is to determine if patients receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT) rather than standard of care will have improvement in symptoms of depression after a course of ECT treatments. The investigators hypothesize that utilization of ketamine for induction of general anesthesia during ECT treatments will improve symptoms of depression better than standard care.

This study is ONLY open to patients eligible to receive healthcare services through the Department of Veterans Affairs at the VA Puget Sound, which means service in the active military, naval or air service or separation under any condition other than dishonorable. Qualifications for VA health care benefits can be found at va.gov.


Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Ketamine Drug: Methohexital Not Applicable

Detailed Description:

The purpose of this prospective randomized clinical trial is to determine if patients receiving ketamine as a part of general anesthesia during electroconvulsive therapy (ECT) rather than standard of care will have improvement in symptoms of depression after a course of ECT treatments. The investigators hypothesize that utilization of ketamine for induction of general anesthesia during ECT treatments will improve symptoms of depression better than standard care.

For induction of general anesthesia for ECT, patients will receive either 1mg/kg of methohexital (standard arm) or 1.0 mg/kg IV ketamine (experimental arm) intravenously (IV) for the duration of their ECT index course over 2-3 weeks. The primary outcome in this trial is change in symptoms of depression assessed by standard questionnaires: Patient Health Questionnaire 9 (PHQ9) and Hamilton Depression Rating Scale (HAM-D) score changes from baseline and final ECT administration. Secondary outcomes are changes in cognitive status as assessed by the Montreal Cognitive Assessment (MoCA) scale, quality of seizures and after seizure, changes in serum metabolites (including kynurenine, D/L-serine and other glutamate intermediates) after treatment and need for further ECT courses (relapse) within 1 year after initial course.

Approximately 50 veterans with the diagnosis of major depressive disorder older than 18 years of age undergoing ECT will be randomized and blinded to the intervention. Operative ECT clinicians will not be blinded; clinicians evaluating patients will be blinded. Exclusion criteria for this study include uncontrolled hypertension, blood pressure > 180/90 mmHg at the pre-anesthesia clinic visit, renal failure, neurologic disorders (e.g. epilepsy, space occupying lesions, traumatic brain injuries in the past 6 months), myocardial infarction in the past 6 months, known allergies or adverse reactions to ketamine, American Society of Anesthesiology Physical Class greater than 3, concomitant psychosis, schizophrenia or current abuse of alcohol or illicit substances and pregnancy.

The long term objective of this trial is to systematically characterize ketamine's effect on depression outcomes utilizing validated scoring tools, its safety profile throughout an ECT index course, ketamine's effect on seizure quality and changes in novel translational endpoints to better understand mechanisms of action of ketamine and its potential role in treatment of psychiatric disorders.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 52 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Ketamine vs. Methohexital Anesthesia for Improvement of Major Depressive Disorder in Electroconvulsive Therapy
Actual Study Start Date : March 2016
Actual Primary Completion Date : April 2017
Actual Study Completion Date : April 30, 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ketamine Interventional Arm
1.0 mg/kg IV ketamine (experimental arm) intravenously (IV) for the duration of their ECT index course over 2-3 weeks
Drug: Ketamine
Ketamine anesthesia for ECT index course with measurement cerebral metabolic regional oximetry, EEG seizure quality, cognitive scoring and serum metabolites.
Other Name: Ketalar

Active Comparator: Methohexital Control Arm
1mg/kg of methohexital (standard arm) intravenously (IV) for the duration of their ECT index course over 2-3 weeks
Drug: Methohexital
Methohexital anesthesia for ECT index course with measurement cerebral metabolic regional oximetry, EEG seizure quality, cognitive scoring and serum metabolites.
Other Name: Brevital




Primary Outcome Measures :
  1. Change in Depression Patient Health Questionnaire 9 (PHQ9) Scoring [ Time Frame: Change from Baseline Score 24 hours prior to starting ECT to PHQ9 score 72 hours following last ECT session ]
    Evaluate the efficacy and safety of repeat anesthetic ketamine dosing during a complete index course of ECT compared with methohexital using change in a validated depression scoring tool (Patient Health Questionnaire 9) administered 24 hours prior to starting an ECT index course treatment (baseline) with a PHQ9 score 72 hours after the last/final ECT session for approximately fifty patients. The PHQ9 Scoring ranges from 0 to 27 in order to monitor depression severity over time for newly diagnosed patients or patients in current treatment for depression.


Secondary Outcome Measures :
  1. Soluble Amino Acid Metabolomic Biomarkers [ Time Frame: 30 minutes prior to first ECT session and within 30 minutes after final ECT session ]
    Measurement of biomarkers before/after ECT index course serum aqueous metabolites from patient venous blood drawn from intravenous line specifically concentration of serine, tryptophan, quinolinic acid, kynurenine in mcg/dL using mass spectrometry. Samples are collected 30 minutes prior to first ECT session and within 30 minutes after final ECT treatment session.

  2. ECT Seizure Duration [ Time Frame: Length of each intraoperative ECT seizure during an index course typically 6-12 individual seizures measure from start of seizure in operating room to end of seizure in operating room. ]
    This trial will measure intra-operative seizure length/duration (in seconds) using a standard ECT machine which helps the ECT machine operator determine the total length of time a patient is seizing during each ECT seizure session. An index course of ECT treatment typically involves 6 to 12 seizures titrated to a patient's response. The investigators will record the length of seizure for every treatment session for every patient.

  3. Change in Montreal Cognitive Assessment (MoCA) Scoring [ Time Frame: Change from Baseline Score 24 hours prior to starting ECT to MoCA score 72 hours following last ECT session ]
    Evaluate the efficacy and safety of repeat anesthetic ketamine dosing during a complete index course of ECT compared with methohexital using change in a validated cognitive scoring tool (Montreal Cognitive Assessment MoCA) administered 24 hours prior to starting an ECT index course treatment (baseline) with a MoCA score 72 hours after the last/final ECT session for approximately fifty patients. The MoCA Scoring ranges from 0 to 30 in order to rapidly screen for mild cognitive dysfunction.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • outpatients or inpatients at the Puget Sound VA with diagnosis of major depressive disorder or bipolar 1 or 2 over the age of 18 undergoing index course ECT

Exclusion Criteria:

  • uncontrolled hypertension (blood pressure > 180/90 mmHg at the pre-anesthesia clinic visit)
  • renal failure
  • neurologic disorders (e.g. epilepsy, space occupying lesions, traumatic brain injuries in the past 6 months)
  • myocardial infarction in the past 6 months
  • known allergies or adverse reactions to ketamine
  • American Society of Anesthesiology Physical Class greater than 3
  • concomitant psychosis
  • schizophrenia or current abuse of alcohol or illicit substances and pregnancy (any trimester)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02752724


Locations
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United States, Washington
VA Puget Sound Health Care System
Seattle, Washington, United States, 98108
Sponsors and Collaborators
VA Puget Sound Health Care System
Investigators
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Study Director: Anna Borisovskaya, MD Puget Sound VA Medical Center, Dept of Psychiatry
Principal Investigator: Irene Rozet, MD Puget Sound VA Medical Center, Dept of Anesthesiology

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Responsible Party: Dr. Charles William Carspecken, MD, MBA, MSc, Physician --Anesthesiologist, VA Puget Sound Health Care System
ClinicalTrials.gov Identifier: NCT02752724     History of Changes
Other Study ID Numbers: 00850
First Posted: April 27, 2016    Key Record Dates
Last Update Posted: June 5, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Dr. Charles William Carspecken, MD, MBA, MSc, VA Puget Sound Health Care System:
major depressive disorder
electroconvulsive therapy
metabolomics
treatment resistant depression
anesthesiology
ketamine
prospective randomized clinical trial
Additional relevant MeSH terms:
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Ketamine
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Anesthetics
Methohexital
Central Nervous System Depressants
Physiological Effects of Drugs
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action