Ketamine Versus Electroconvulsive Therapy in Depression
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|ClinicalTrials.gov Identifier: NCT03674671|
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : October 7, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Depressive Disorder, Major Bipolar Depression||Drug: Intravenous Ketamine Procedure: Electroconvulsive Therapy||Phase 3|
Worldwide, depression carries a significant burden. Although there are effective treatments for depression, many patients do not achieve remission, and any significant response usually occurs after a few weeks. The common approach for a rapid intervention in cases of severe depressive symptoms has been electroconvulsive therapy (ECT). There are drawbacks to ECT including a prior medical work-up, general anaesthesia, and the possibility of memory loss. Further, access to ECT is often limited. Comparatively, the most striking breakthrough in the field of mood disorders has been the rapid antidepressant effects of intravenous ketamine. The antidepressant response to ketamine often occurs within a few hours, and peaks within 24. Recent studies have documented that the benefits of ketamine can be sustained with repeated administration.
This longitudinal, multi-centre, randomized, crossover clinical trial is funded in part by the Ontario Brain Institute through a sponsorship with the Canadian Biomarker Integration Network in Depression (CAN-BIND) research program. It will take place across five sites: the Royal Ottawa Mental Health Centre (lead site), Douglas Mental Health University Institute, Providence Care Hospital, Sunnybrook Health Sciences Centre and University Health Network.
A total of 240 participants (accounting for 20% dropout) will be recruited over 30 months from ECT wait lists across the five sites and randomized to either the ketamine or ECT treatment arm. Participants in the ketamine treatment arm will receive 0.5 mg/kg IV over 40 minutes in the recovery room of the ECT clinic as per the study schedule. Participants in the ECT treatment arm will receive ECT as per the study schedule and as decided by their treating physician. Each participant will be enrolled in the study for between six weeks and nine months, or until they leave the study or the study is terminated.
Throughout the study, clinical, neuroimaging, molecular, and cognitive assessments will be conducted. Data will be collected using the Ontario Brain Institute's Centre for Ontario Data Exploration and Research Electronic Data Capture in order to coordinate data from the five sites.
Participants randomized to the either treatment arm will receive thrice weekly treatments for 3 or 4 weeks for a total of 9 or 12 treatments respectively. Following the randomization phase, responders may move to the maintenance phase and non-responders may move to the crossover phase where they will receive the alternate therapy. During the crossover phase, participants will receive thrice weekly treatments for 3 or 4 weeks for a total of 9 or 12 treatments respectively. Following the crossover phase, responders will move to the maintenance phase and non-responders will exit the study. During the maintenance phase, participants who achieved response with ketamine will receive weekly ketamine treatments for one month, treatment once every two weeks for two months, and monthly treatment for three months. Should participants in the ketamine arm relapse during monthly treatment, they may return to treatments once every two weeks. Participants who achieved response in the ECT arm will receive ECT treatment for six months based on decision of the treating physician in order to maintain a clinical response. Both treatment arms will have a follow-up visit during month seven.
The aim of this study is to show that compared to ECT, ketamine treatment produces faster therapeutic action, has less side effects, requires fewer/shorter hospitalizations for patients, and will be less expensive because it does not require an anaesthesiologist and a psychiatrist to administer the various ECT protocols. Through the discovery of biomarkers to predict ECT or ketamine response or non-response, the anticipated effective treatment could be administered as a first line intervention for a subgroup of depressed patients, thereby ensuring a more time-efficient intervention.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||240 participants|
|Intervention Model:||Crossover Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Investigations on the Efficacy of Ketamine in Depression in Comparison to Electroconvulsive Therapy|
|Actual Study Start Date :||October 29, 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
|Experimental: Intravenous Ketamine||
Drug: Intravenous Ketamine
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.
Other Name: Ketalar
|Active Comparator: Electroconvulsive Therapy||
Procedure: Electroconvulsive Therapy
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.
Other Name: ECT
- Montgomery-Asberg Depression Rating Scale [ Time Frame: 3-4 weeks ]
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
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): NCT03674671
|Contact: Ubah Mohamed, RPN||613-722-6521 ext firstname.lastname@example.org|
|Contact: Maria DaSilva||613-722-6521 ext email@example.com|
|Providence Care Hospital||Recruiting|
|Kingston, Ontario, Canada, K7M 9A7|
|Contact: Emily Hawken, PhD firstname.lastname@example.org|
|Principal Investigator: Roumen Milev, MD, PhD|
|Sub-Investigator: Gustavo Vazquez, MD, PhD|
|Royal Ottawa Mental Health Centre||Recruiting|
|Ottawa, Ontario, Canada, K1Z 7K4|
|Contact: Ubah Mohamed, RPN 613-722-6521 ext 7828 email@example.com|
|Principal Investigator: Pierre Blier, MD, PhD|
|Sub-Investigator: Jennifer L Phillips, PhD|
|Sub-Investigator: Natalia Jaworska, PhD|
|Sub-Investigator: Lisa McMurray, MD|
|Sub-Investigator: Jean Blier, MD|
|Sunnybrook Health Sciences Centre||Not yet recruiting|
|Toronto, Ontario, Canada, M4N 3M5|
|Contact: Anusha Baskaran, PhD 416-480-6100 ext 1650 firstname.lastname@example.org|
|Contact: Sachie Sharma 416-480-6100 ext 3254 email@example.com|
|Principal Investigator: Peter Giacobbe, MD|
|University Health Network||Recruiting|
|Toronto, Ontario, Canada, M5G 1J6|
|Contact: Franca Placenza, PhD 416-603-5800 ext 8839 firstname.lastname@example.org|
|Principal Investigator: Sidney Kennedy, MD|
|Sub-Investigator: Shane McInerney, MD|
|Sub-Investigator: Venkat Bhat, MD|
|Sub-Investigator: Susan Rotzinger, PhD|
|Sub-Investigator: Jane Foster, PhD|
|Sub-Investigator: Jonathan Downar, MD, PhD|
|Sub-Investigator: Alastair Flint, MB|
|Sub-Investigator: Gerald O'Leary, MB|
|Sub-Investigator: Karim Ladha, MD|
|Douglas Mental Health University Institute||Not yet recruiting|
|Verdun, Ontario, Canada, H4H 1R3|
|Principal Investigator: Gustavo Turecki, MD, PhD|
|Sub-Investigator: Stéphane Richard-Devantoy, MD, PhD|
|Principal Investigator:||Pierre Blier, MD, PhD||The Royal's Institute of Mental Health Research|