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Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy

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ClinicalTrials.gov Identifier: NCT02579642
Recruitment Status : Unknown
Verified May 2018 by Ferrante Gragasin, University of Alberta.
Recruitment status was:  Enrolling by invitation
First Posted : October 19, 2015
Last Update Posted : May 3, 2018
Sponsor:
Collaborator:
Alberta Health Services
Information provided by (Responsible Party):
Ferrante Gragasin, University of Alberta

Tracking Information
First Submitted Date  ICMJE October 13, 2015
First Posted Date  ICMJE October 19, 2015
Last Update Posted Date May 3, 2018
Study Start Date  ICMJE October 2015
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 15, 2015)
Number of treatments to achieve 50% change (reduction) in Montgomery Ashberg Depression Rating Scale (MADRS) [ Time Frame: 6 weeks ]
Defined a priori as "response". Assessed at baseline, 24 hours after ECT treatments for the duration of the study and then once at 6 weeks.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 15, 2015)
  • Number of treatments to achieve 25% change (reduction) in MADRS [ Time Frame: 6 weeks ]
    Defined a priori as "partial response". Assessed at baseline, 24 hours after ECT treatments for the duration of the study and then once at 6 weeks.
  • Change in Clinical Global Impression - Severity (CGI-S) scores [ Time Frame: 6 weeks ]
    Assessed at baseline, 24 hours after ECT treatments for the duration of the study and then once at 6 weeks.
  • Changes in blood pressure seen during ECT [ Time Frame: 4 weeks ]
    Measured during ECT treatments and in the post-ECT recovery room.
  • Changes in heart rate seen during ECT [ Time Frame: 4 weeks ]
    Measured during ECT treatments and in the post-ECT recovery room.
  • Changes in oxygen saturation seen during ECT [ Time Frame: 4 weeks ]
    Measured during ECT treatments and in the post-ECT recovery room.
  • Changes in respiratory rate seen during ECT [ Time Frame: 4 weeks ]
    Measured during ECT treatments and in the post-ECT recovery room.
  • Changes in times to discharge from post-ECT recovery [ Time Frame: 4 weeks ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: October 15, 2015)
Changes in seizure duration during ECT [ Time Frame: 4 weeks ]
As measured by clinical/visual assessment as well as by EEG.
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy
Official Title  ICMJE Effects of Low-dose Ketamine as an Adjunct to Propofol-based Anesthesia for Electroconvulsive Therapy
Brief Summary

Ketamine has been used successfully as the sole medication for anesthesia in the setting of electroconvulsive therapy (ECT), and has more recently been studied as an adjunct agent in combination with propofol (the most commonly used anesthetic agent) to induce anesthesia for ECT. New literature postulates an anti-depressant effect of ketamine, which in ECT specifically may be helpful with regards to the overall goals of therapy (i.e. ECT indicated for severe or treatment-resistant depression).

Current research focusing on ketamine with respect to its anti-depressant effect suggests it may even represent an alternative to ECT. This study will seek to determine whether ketamine when used in low-doses as an adjunct to propofol-based anesthesia for ECT has anti-depressant effects and whether it influences the characteristics of recovery from anesthesia in the ECT setting (i.e. vital sign parameters such as blood pressure and heart rate, quality of recovery, etc.).

Detailed Description

This is a proof-of-concept study to elucidate whether the use of low-dose ketamine as an adjunct to propofol-based anesthesia for electroconvulsive therapy has beneficial anti-depressant effects in a population of adults with major depressive disorder presenting for ECT.

Since thiopental is no longer widely available in North America as an induction agent for anesthesia, other agents have supplanted it for various uses, including for induction of anesthesia for electroconvulsive therapy (ECT). Induction is most commonly achieved using propofol in doses of 0.75 - 1 mg/kg IV bolus.

Propofol as an induction agent for ECT may not be the ideal agent in this setting as its anticonvulsant effects may result in less-than-ideal seizure quality and duration. Ketamine has been studied in the ECT setting but at full induction doses has well-known psychotomimetic and dissociative effects. However, the anti-depressant effects of ketamine, even at low-doses, may have a beneficial effect on depressive symptoms after ECT as compared with propofol alone.

Ketamine also has been used successfully as the sole induction agent for anesthesia in this setting, and has more recently been studied as an adjunct or co-induction agent in combination with propofol. Drawbacks of using ketamine as the sole induction agent are related to its hemodynamic and psychotomimetic effects (e.g. post-treatment hypertension and hallucinogenic activity).

New literature postulates a putative anti-depressant effect of ketamine via the N-Methyl-D-aspartate (NMDA) receptor, which in the ECT setting specifically may be helpful with regards to the overall goals of therapy (i.e. ECT indicated for severe or treatment-resistant depression). Current research focusing on the efficacy of ketamine with respect to anti-depressant effects suggests that ketamine may even represent an alternative to ECT.

As per the investigators' standard practice for ECT, treatment for each patient would be 3 times per week up to a total of 12 treatments (i.e. 4 weeks of treatment). The total study duration for each patient will be not more than 6 weeks. As discussed below, patients will be withdrawn from the study at anytime upon their own request or when the treating psychiatrist feels the clinical improvement is strong enough to justify doing so.

An interim analysis will be completed after the first 14 patients have completed treatment. If after these first 14 patients the investigators find a lower than expected difference in efficacy in favor of the ketamine group, able to achieve alpha error >0.2 and power <80%, all subsequently recruited patients will be randomized to receive either propofol at usual induction doses for ECT (0.75 - 1 mg/kg IV bolus) with placebo (normal saline), or with a slightly higher dose of ketamine of 0.5 mg/kg. Should this turn out to be the case, thirty new patients will be recruited from that point.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Depressive Disorder
Intervention  ICMJE
  • Drug: Ketamine
    Low dose ketamine 0.2 mg/kg (or 0.5 mg/kg depending on results of interim analysis) administered with usual induction drugs for ECT
    Other Name: Ketalar
  • Drug: Placebo
    Normal saline administered with usual induction drugs for ECT
    Other Names:
    • Normal saline
    • 0.9% NS
Study Arms  ICMJE
  • Placebo Comparator: Placebo
    Propofol at usual induction doses for ECT (0.75 - 1 mg/kg IV bolus) with placebo (normal saline)
    Intervention: Drug: Placebo
  • Experimental: Ketamine
    Propofol at usual induction doses for ECT (0.75 - 1 mg/kg IV bolus) with the addition of low-dose ketamine 0.2 mg/kg (or 0.5 mg/kg - see interim analysis)
    Intervention: Drug: Ketamine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: October 15, 2015)
44
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 2019
Estimated Primary Completion Date May 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • referred for ECT with a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of major depressive disorder
  • considered American Society of Anesthesiologists (ASA) Physical Class I - III
  • baseline MADRS score greater than 24 (i.e. at least moderate to severe depression)
  • a "first" or "new" episode of depression which has lasted not more than 3 months and requires ECT treatment as judged by a psychiatrist

Exclusion Criteria:

  • ASA Class IV or V as judged by the anesthesiologist
  • Any ECT treatment in the previous three months
  • Inability or refusal to provide informed consent
  • A history of allergic reactions, hypersensitivity, or intolerance to anesthetics or their constituents used in the study (ketamine, propofol, egg phosphatide, soybean oil)
  • Anyone taking medications considered contraindicated for ECT or for general anesthesia
  • Presence of any of the following DSM-IV diagnoses: Substance or alcohol dependence at enrolment (except dependence in full remission, and except for caffeine or nicotine dependence), abuse of opiates, amphetamines, barbiturates, cocaine, cannabis, or hallucinogen abuse in the 4 weeks prior to enrolment, pervasive developmental disorder, dementia
  • Significant medical condition that would contraindicate the use of ketamine, propofol or that is untreated and would need urgent attention (as determined by treating physician)
  • Medical conditions that would significantly affect absorption, distribution, metabolism, or excretion of ketamine or propofol
  • Unstable or inadequately treated medical illness (e.g. congestive heart failure, angina pectoris, hypertension) as judged by the investigator
  • Patients with increased risk of laryngospasm (such as active pulmonary infection, upper respiratory infection, asthma), increased intracranial pressure, glaucoma, thyroid disease/hyperthyroidism
  • Any clinically significant deviation from the reference range in clinical laboratory test results as judged by the investigator
  • Pregnancy (or female of child-bearing age not using adequate contraception) or lactation
  • Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02579642
Other Study ID Numbers  ICMJE PRO00044771
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ferrante Gragasin, University of Alberta
Study Sponsor  ICMJE University of Alberta
Collaborators  ICMJE Alberta Health Services
Investigators  ICMJE
Principal Investigator: Ferrante S Gragasin, MD, PhD University of Alberta
PRS Account University of Alberta
Verification Date May 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP