Ketamine Versus Electroconvulsive Therapy in Depression

NCT03674671 | Suspended Phase 3 DMC

• 1 other identifier: REB2018007
• Study Type: interventional
• Target: 240
• Locations: 1 country
• Sites: 4

Brief Summary

While there are effective treatments for depression available, some patients do not see results with these options. Often, these patients are referred to electroconvulsive therapy (ECT) which has drawbacks such as adverse side effects, cost, and limited access. Recent research shows that intravenous ketamine may be an alternative option for these patients due to its rapid antidepressant effect sustained with multiple treatments. This study will recruit 240 participants from the ECT waiting list at the five participating hospitals, and randomize them to either the ketamine or ECT treatment arm. Participants in the ketamine treatment arm will receive 0.5mg/kg ketamine intravenously (IV) over 40 minutes as described in the study schedule. Participants in the ECT treatment arm will receive ECT as described in the study schedule and as decided by their treating physician. Throughout the study, clinical, neuroimaging, molecular, and cognitive assessments will be conducted. The aim of this study is to show that compared to ECT, ketamine treatment produces faster results, has less side effects, requires less or shorter hospitalizations, and is less expensive. The measures collected throughout the study (clinician scales, self-reports, blood samples, and neuroimaging) may help with predicting if future patients will respond to ECT or ketamine. This could lead to faster, more effective treatment for patient with depression.

Conditions

Depressive Disorder, Major; Bipolar Depression

Keywords

Depression; MDD; neuroimaging; biomarkers; genomics; proteomic; BP

Outcome Measures

Primary Outcomes (1)

• Montgomery-Asberg Depression Rating Scale

  Change in MADRS (Montgomery-Asberg Depression Rating Scale) scores from baseline. * Remission: MADRS ≤ 10 * Response: \>50% reduction in MADRS from baseline and a score \<22

  3-4 weeks

Study Arms (2)

Intravenous Ketamine

EXPERIMENTAL

Drug: Intravenous Ketamine

Electroconvulsive Therapy

ACTIVE COMPARATOR

Procedure: Electroconvulsive Therapy

Interventions

Intravenous Ketamine DRUG

Participants will receive 0.5mg/kg IV over 40 minutes, thrice weekly for 3 or 4 weeks. If participant responds, they will receive infusions weekly for one month, once every two weeks for two months, and once every month for three months. Should participant relapse during once monthly dosing, they may return to dosing once every two weeks for the remainder of the study.

Also known as: Ketalar

Intravenous Ketamine

Electroconvulsive Therapy PROCEDURE

Participants will receive ECT treatment thrice weekly for the 3 or 4 weeks. If participant responds, they will continue to receive ECT, with frequency at the discretion of the treating physician based on best practice guidelines for the remainder of the study.

Also known as: ECT

Electroconvulsive Therapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of written informed consent before initiation of any study-related procedures.
• Eligible subjects who have consented to standard ECT treatment for their mood disorder and are willing to accept randomization to either ECT or IV ketamine group.
• Men and women aged between 18 and 70 years, inclusive with a body mass index (BMI) \< 35. They must have a Montreal Cognitive Assessment (MOCA) score ≥ 24.
• Patients meeting criteria for Major Depressive Disorder (MDD) or Bipolar Disorder (BP) without psychotic symptoms according to the Diagnostic and Statistical Manual for Mental Disorders (DSM-5) currently in a Major Depressive Episode (MDE) as confirmed by the MINI International Neuropsychiatric Interview (MINI).
• A Montgomery-Åsberg Depression Rating Scale (MADRS) total score of ≥ 26 at screening and at randomization, with no more than 20% improvement between these two visits.
• Female subjects of childbearing potential must have a negative urine pregnancy test at enrolment (Visit 1) and be willing to use a reliable method of birth control (i.e., double-barrier method, oral contraceptive, implant, dermal contraception, long-term injectable contraceptive, intrauterine device, or tubal ligation) during the study.
• Abstain from consuming grapefruit juice (a potent 3A4 cytochrome inhibitor) on the day of the ketamine infusions as it may slow down the elimination of ketamine.
• Be able to understand and comply with the requirements of the study, as judged by the investigator(s).

You may not qualify if:

• Depression secondary to stroke, cancer or other severe medical illnesses.
• Prior or current substance abuse or dependence (except for caffeine or nicotine dependence) and/or recent history (last 12 months) of current alcohol abuse or dependence, as defined in DSM-5 criteria ("a problematic pattern of using alcohol or another substance that results in impairment in daily life or noticeable distress").
• A positive toxicology screen for drugs that are not prescribed.
• Unwilling to maintain current antidepressant regimen.
• Unwilling or unable to hold benzodiazepines from the evening prior to the infusion of ketamine.
• Unwilling to discontinue any narcotic for a minimum of 5 drug half-lives prior to injections.
• Pregnant, lactating, or of childbearing potential and not willing to use an approved method of contraception during the study.
• Evidence of clinically relevant disease, e.g., uncontrolled hypertension, renal or hepatic impairment, significant coronary artery disease (myocardial infarct within a year prior to initial randomization), cerebrovascular disease, history of cerebrovascular accident, viral hepatitis B or C, acquired immunodeficiency syndrome.
• A clinical finding that is unstable or that, in the opinion of the investigator(s), would be negatively affected by the study medication or that would affect the study medication (e.g., diabetes mellitus, hypertension, unstable angina).
• Liver function tests AST and ALT three times the upper normal limit at screening.
• Uncorrected hypothyroidism or hyperthyroidism. Subjects needing a thyroid hormone supplement to treat hypothyroidism must have been on a stable dose of the medication for 30 days prior to enrolment (Visit 1).
• Clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator(s). Including:
• Sodium under 135 or over 145 mmol/L
• Potassium under 3.5 or over 5.0 mmol/L
• Chloride under 98 or over 106 mmol/L

Sponsors & Collaborators

• University of Ottawa: lead
• McGill University: collaborator
• Queen's University: collaborator
• University Health Network, Toronto: collaborator
• Ontario Shores Centre for Mental Health Sciences: collaborator

Study Sites (4)

Providence Care Hospital

Kingston, Ontario, K7M 9A7, Canada

Location

Royal Ottawa Mental Health Centre

Ottawa, Ontario, K1Z 7K4, Canada

Location

University Health Network

Toronto, Ontario, M5G 1J6, Canada

Location

Ontario Shores Centre for Mental Health Sciences

Whitby, Ontario, L1N 5S9, Canada

Location

Related Publications (1)

• Phillips JL, Jaworska N, Kamler E, Bhat V, Blier J, Foster JA, Hassel S, Ho K, McMurray L, Milev R, Moazamigoudarzi Z, Placenza FM, Richard-Devantoy S, Rotzinger S, Turecki G, Vazquez GH, Kennedy SH, Blier P; CAN-BIND Investigator Team. A randomized, crossover comparison of ketamine and electroconvulsive therapy for treatment of major depressive episodes: a Canadian biomarker integration network in depression (CAN-BIND) study protocol. BMC Psychiatry. 2020 Jun 2;20(1):268. doi: 10.1186/s12888-020-02672-3.

  PMID: 32487236 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major; Bipolar Disorder; Depression

Interventions

Ketamine; Electroconvulsive Therapy

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Convulsive Therapy; Psychiatric Somatic Therapies; Behavioral Disciplines and Activities; Electroshock; Psychological Techniques

Study Officials

• Pierre Blier, MD, PhD

  The Royal's Institute of Mental Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Endowed Chair and Director, Mood Disorders Research Unit

Study Record Dates

• First Submitted: July 6, 2018
• First Posted: September 17, 2018
• Study Start: October 29, 2018
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

CA (4)