ECT with Ketamine Anesthesia Vs High Intensity Ketamine with ECT Rescue for Treatment-Resistant Depression

NCT03272698 | Recruiting Phase 4 DMC FDA Drug

• 1 other identifier: 123456
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 1

Brief Summary

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)

Conditions

Treatment Resistant Depression; Ketamine

Keywords

ketamine; treatment-resistant depression; electroconvulsive therapy

Outcome Measures

Primary Outcomes (1)

• Number of treatments required to reach disease remission

  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 Outcomes (5)

• Rate of rescue ECT in the HIKER arm

  From date of randomization up to 6 days

• Suicidal ideation

  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

  MMSE will be assessed at baseline, final treatment, and 30 day post-treatment follow-up

• Self- and clinician rated improvement

  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

  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

Study Arms (2)

Ketamine (HIKER)

EXPERIMENTAL

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

Ketamine-ECT (EAST)

ACTIVE COMPARATOR

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; Procedure: ECT

Interventions

Ketamine DRUG

IV Ketamine 0.50 mg/kg

Also known as: Ketalar

Ketamine (HIKER); Ketamine-ECT (EAST)

ECT PROCEDURE

ECT with unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method

Ketamine-ECT (EAST)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Saskatchewan: lead
• Royal University Hospital Foundation: collaborator

Study Sites (1)

Royal University Hospital

Saskatoon, Saskatchewan, S7N 0W8, Canada

RECRUITING

Related Publications (17)

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  PMID: 17444078 BACKGROUND

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  PMID: 11941041 BACKGROUND

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  PMID: 20051218 BACKGROUND

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  BACKGROUND

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  BACKGROUND

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  BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Jonathan Gamble, MD

  University of Saskatchewan

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Una Goncin

CONTACT

3066551183; ung039@usask.ca

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Patients will be randomized to either the HIKER or EAST arms, but due to the different frequencies of treatment, patient and physician blinding will not be possible. Outcome assessor will also not be blinded. As patients were not blinded, they could easily divulge their treatment allocation. The outcome assessor can also deduce treatment allocation from communications with nursing staff or study personnel. However, the follow up assessment at 30 days post-final treatment will be performed by a different study team member who will remain blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D.

Model Details: Patients in the EAST arm will receive eight ECT sessions (on a bi/triweekly schedule, weekdays only) with ketamine-based general anesthetic (ketamine 0.75 mg/kg, remifentanil 1 mcg/kg, and succinylcholine 0.75 mg/kg for safety. Patients in the HIKER arm will receive a single dose of ketamine 0.50 mg/kg, on 8 successive weekdays. Since ketamine without ECT is not the standard of care for TRD, patients in the HIKER arm who do not achieve a 25% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) after the third treatment will be deemed non-responsive to ketamine and switched to a standard 8 treatment course of ECT with ketamine-based GA as described in the EAST arm - this will be called rescue ECT. The attending psychiatrist may discontinue therapy for either arm if the patient achieves remission or treatment is ineffective based on clinical judgment.

Study Record Dates

• First Submitted: August 28, 2017
• First Posted: September 5, 2017
• Study Start: September 1, 2017
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: January 23, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)