ECT With Ketamine Anesthesia vs High Intensity Ketamine With ECT Rescue for Treatment-Resistant Depression

December 19, 2023 updated by: Jonathan Gamble, University of Saskatchewan

A Prospective Randomized Controlled Trial of Electroconvulsive Therapy With Ketamine Anesthesia (Standard Therapy) and High Intensity Ketamine With Electroconvulsive Therapy Rescue for Treatment-Resistant Depression - EAST HIKER Trial

To determine if an high intensity ketamine with ECT rescue (HIKER) approach for treatment resistant depression will: 1) reduce patient suffering by hastening disease remission, 2) have fewer side effects, 3) reduce the need for ECT, and 4) be preferred by most patients. Half of participants will be randomized to the HIKER arm and receive high intensity ketamine treatment for eight consecutive days, and the other half will be assigned to the ECT with ketamine anesthesia (EAST) arm and receive 8 ECT treatments (2-3 treatment/week)

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Major depressive disorder (MDD) is a common psychiatric illness that will affect at least 15% of the population. The burden of MDD is staggering, considered by the World Health Organization to be the leading cause of disability in developed countries for people aged 15-44.

Oral antidepressant therapy for MDD is notoriously ineffective. At least 3 weeks of treatment is usually required to achieve response rates that rarely exceed 40% (only 10% better than placebo); furthermore, treatment can be complicated by serious side effects serious (e.g. falls, weight gain) including increased suicidality. Up to 15% of patients will eventually be diagnosed as having treatment-resistant depressions (TRD), defined as the failure to respond to at least two antidepressants from different pharmacologic classes after adequate treatment duration at therapeutic dosages. The gold standard therapy for TRD is electroconvulsive therapy (ECT) with general anaesthesia (GA), which produces rapid antidepressant effects after only a few sessions. Propofol is the traditional anaesthetic agent used in GA for ECT, although recently this research group showed that ECT with ketamine as the primary anaesthetic produced faster depression remission compared to ECT with propofol.

Despite its efficacy, ECT is associated with considerable problems. More than 10% of patients will experience amnesia and confusion, which can persist for weeks. These cognitive side effects limit the frequency of ECT treatments to two or three times per week. There is also a risk of rare but devastating cardiorespiratory adverse events, at least part of which can be attributed to the need to induce chemical paralysis (for safety) and administer opioids (for pain control) during ECT with GA. Lastly, ECT requires specialized psychiatric expertise, dedicated resources, specially trained nurses, and an anaesthesiologist - requirements that are both costly and not readily available in many settings.

In contrast to ECT, daily short-acting anaesthesia, including ketamine, is well tolerated. A recent study found that only three treatments of intravenous ketamine produced a greater early improvement in depression scores compared to ECT under non-ketamine-based GA. This suggests a possibility of achieving early disease remission in TRD with ketamine-only infusions while avoiding the safety risks and treatment delays associated with ECT under GA.

The efficacy, feasibility, and improved side-effect profile of frequent successive ketamine treatments suggest it may be the preferred treatment for TRD compared to ECT with ketamine-based GA. There may, however, be a small subgroup of TRD patients who do not respond to ketamine alone and require ECT, although with a daily treatment regimen, ketamine non-responders could be quickly identified and given a standard course of ECT. The researchers propose that a treatment protocol of daily High Intensity Ketamine with ECT Rescue (HIKER) will be superior to ECT Therapy with ketamine anesthesia standard therapy (EAST) in facilitating early disease remission, while at the same time yielding similar overall remission rates by allowing ketamine non-responders to be quickly identified and given ECT.

Study Type

Interventional

Enrollment (Estimated)

62

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Canada
    • Saskatchewan
      • Saskatoon, Saskatchewan, Canada, S7N 0W8
        • Recruiting
        • Royal University Hospital
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Montgomery Asberg Depression Rating Scale (MADRS) score of greater than 20) planned for ECT therapy.
  • Subjects must meet clinical criteria for TRD defined as failure to respond to at least 2 standard-of-care drug therapies of adequate treatment duration.

Exclusion Criteria:

  • Subjects will be ineligible if they cannot provide informed consent
  • American Society of Anesthesiology physical status score of four or greater
  • Implanted medical device with electronic parts (e.g. pacemaker, defibrillator, intrathecal pump, spinal cord stimulator, deep brain stimulator)
  • Schizoaffective disorder
  • Women of child-bearing potential will be asked to undergo a commercial urine pregnancy screening test. Those who refuse or screen positive will be excluded.
  • Allergic to any of the study drugs or their carrier components
  • Any serious physical condition prior to randomization deemed by the attending psychiatrist or consulting anesthetist to be a contraindication to ECT such as cardiovascular disease (including untreated hypertension), respiratory disease, cerebrovascular disease, intracranial hypertension (including glaucoma), or seizures.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ketamine (HIKER)
Patients in the HIKER arm will receive a single dose of ketamine 0.50 mg/kg, which is enough to achieve a full anaesthetic effect (i.e., unconsciousness mimicking the GA regimen above), on 8 successive weekdays.
Drug: Ketamine
IV Ketamine 0.50 mg/kg
Other Names:
  • Ketalar
Active Comparator: Ketamine-ECT (EAST)
Patients in the EAST arm will initially receive intravenous ketamine 0.75 mg/kg, remifentanil 1 mcg/kg (to reduce discomfort), and succinylcholine 0.75 mg/kg (for safety). Based on patients' anaesthetic response, the attending anaesthesiologist is given the freedom to vary the dose of remifentanil and succinylcholine as well as administer propofol to achieve safe and acceptable anaesthetic conditions. As per the Saskatoon Health Region's care standard, patients in the EAST arm will receive eight ECT sessions (on a bi/triweekly schedule) delivered by the attending psychiatrist with either unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method.
Drug: Ketamine
IV Ketamine 0.50 mg/kg
Other Names:
  • Ketalar
Procedure: ECT
ECT with unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of treatments required to reach disease remission
Time Frame: From date of randomization until the date of disease remission or after 8 treatments, assessed up to 4 weeks
The primary outcome is number of treatments required to reach disease remission, as defined by a reduction of MADRS score to under 10
From date of randomization until the date of disease remission or after 8 treatments, assessed up to 4 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of rescue ECT in the HIKER arm
Time Frame: From date of randomization up to 6 days
Percent of patients in the HIKER arm who do not achieve a 25% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) after the third treatment.
From date of randomization up to 6 days
Suicidal ideation
Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks
Suicidal ideation as measured by the Columbia Suicide Severity Rating Scale
From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks
Cognitive Impairment
Time Frame: MMSE will be assessed at baseline, final treatment, and 30 day post-treatment follow-up
Cognitive Impairment as measured by Mini-Mental State Exam (MMSE)
MMSE will be assessed at baseline, final treatment, and 30 day post-treatment follow-up
Self- and clinician rated improvement
Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks
Patients will rate their condition on the patient-rated clinical global impression - improvement scale (PGI-I)
From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks
Patient satisfaction with treatment
Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks
Satisfaction with treatment will be assessed by the 2-item treatment satisfaction questionnaire for medication-version II (TSQM-GS-II).
From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Saskatchewan

Collaborators

Royal University Hospital Foundation

Investigators

  • Principal Investigator: Jonathan Gamble, MD, University of Saskatchewan

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2017

Primary Completion (Estimated)

December 30, 2024

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

August 28, 2017

First Submitted That Met QC Criteria

September 1, 2017

First Posted (Actual)

September 5, 2017

Study Record Updates

Last Update Posted (Actual)

December 20, 2023

Last Update Submitted That Met QC Criteria

December 19, 2023

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 123456 (UMMashhad)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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