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N-methyl-D-aspartate Antagonist (Ketamine) Augmentation of Electroconvulsive Treatment for Severe Major Depression

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ClinicalTrials.gov Identifier: NCT01260649
Recruitment Status : Terminated (lack of funding to cover staff salary (clinician and research coordinator))
First Posted : December 15, 2010
Results First Posted : April 14, 2017
Last Update Posted : May 22, 2017
Sponsor:
Information provided by (Responsible Party):
Cristina Cusin, MD, Massachusetts General Hospital

Tracking Information
First Submitted Date  ICMJE December 7, 2010
First Posted Date  ICMJE December 15, 2010
Results First Submitted Date  ICMJE March 3, 2017
Results First Posted Date  ICMJE April 14, 2017
Last Update Posted Date May 22, 2017
Actual Study Start Date  ICMJE November 1, 2010
Actual Primary Completion Date October 26, 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
Change in Hamilton Depression Rating Scale - 28 [ Time Frame: baseline, one month ]
HAMD will be administered at every ECT treatment.The HAM D 28 is a 28 item scale with scores ranging from 0 to 83, with 0 being no depression and 83 being high levels of depression symptoms. The change in HAM S score was determined by the difference of the HAM D score at the last ECT administration and the baseline HAM D score. A negative change score reflects a decreased HAM D score between the first and last ECT administration and therefore a reduction in depressive symptoms.
Original Primary Outcome Measures  ICMJE
 (submitted: December 14, 2010)
Hamilton Depression Rating scale - 28 [ Time Frame: one month ]
HAMD will be administered at every ECT treatment, and 7-10 days after last ECT (approximately 1 month after baseline)
Change History Complete list of historical versions of study NCT01260649 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2017)
Number of Participants With Cognitive Side Effects [ Time Frame: 3 months ]
will compare the incidence of participants with memory deficits between groups, as determined by incidents of clinician reported cognitive adverse events
Original Secondary Outcome Measures  ICMJE
 (submitted: December 14, 2010)
Cognitive Side Effects [ Time Frame: 3 months ]
will compare the incidence and severity of memory deficits between groups, as compound score deriving from memory tests (from Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), from Letter number sequencing and from Autobiografic Memory Interview.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE N-methyl-D-aspartate Antagonist (Ketamine) Augmentation of Electroconvulsive Treatment for Severe Major Depression
Official Title  ICMJE Not Provided
Brief Summary

Electroconvulsive therapy (ECT), is considered the most effective treatment for severe treatment resistant major depressive disorder (MDD), but it requires about 3 weeks of treatments and can cause considerable acute deficits in memory. It would be a major advance in treatment if ECT could work faster with fewer treatments and result in decrease incidence of memory problems. Ketamine is an excellent candidate for augmentation of ECT because of its acute effects on depression, its short half-life, and its safety profile when given at low doses. Ketamine is given as an infusion and could easily be incorporated into the routine management of patients undergoing ECT, but has never been evaluated prospectively in this context.

The investigators propose to assess the efficacy, feasibility, tolerability and safety of N-methyl-D-aspartate antagonist augmentation of ECT using ketamine.

Detailed Description

Aim #1: To assess the efficacy of ketamine augmentation in reducing time to remission of a major depressive episode (MDE).

Aim #2: To assess the efficacy of ketamine augmentation on ECT-related cognitive side effects.

Aim #3: To assess the feasibility, safety, and tolerability of ketamine augmentation of ECT.

Exploratory aim #4: We propose to assess the patterns of functional connectivity before, during and after ECT using standard clinical EEG to better characterize the effect of ECT and to correlate clinical effects with changes in EEG measurements.

Thirty (30) participants will be recruited over 24 months. Participants will be males and females, ages 18-60, with severe MDD (baseline score HAM_D-28 >= 20) deemed appropriate for ECT treatment by their treating physician, agreeing to receive ECT treatment as part of their clinical care, and able to provide informed consent.

Exclusion criteria are any other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia, any history of psychosis, substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence, organic mental disorders, seizure disorder or chronic antiepileptic medications, severe or unstable medical illness, pregnancy.

Study procedures: eligible patients will be randomized to a double-blind administration of ketamine (0.5 mg/kg) or saline before the first three ECT treatments. Right Unilateral ECT (RUL-ECT) will be administered at 6 times the seizure threshold, using the d'Elia placement of the electrodes. Electroconvulsive therapy will be given 3 times per week, as per standard of care at MGH. Depression severity will be assessed weekly with the HAM-D 28 (the main outcome measure), administered by a clinician blinded to randomization.

The neuropsychological assessment battery is designed to include instruments sensitive to the cognitive impairment associated with depression in general and ECT treatment in particular will be repeated at baseline, at the end of acute treatment series and at 3 months follow-up.

Also patients will undergo repeated EEG monitoring, at baseline after one week of treatment and at follow up with the aim of possibly identifying EEG features associated with response.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE
  • Drug: ketamine
    eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care
  • Other: IV Saline
    eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg) or IV Saline, followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care
  • Procedure: ECT
    ECT will be administered as per standard of care
  • Drug: Muscle Relaxant
    All participant will receive routine course of muscle relaxant with ECT as per standard of care
  • Drug: Anesthetic Agents
    All participant will receive routine course of anesthetic agents with ECT as per standard of care
Study Arms  ICMJE
  • Experimental: ketamine
    ketamine (0.5 mg/kg) followed by anesthetic agent titrated to sedation and succinylcholine titrated to muscle relaxation Right unilateral ECT at 5-6x seizure threshold three times a week
    Interventions:
    • Drug: ketamine
    • Procedure: ECT
    • Drug: Muscle Relaxant
    • Drug: Anesthetic Agents
  • Placebo Comparator: placebo

    IV saline, followed by anesthestic agent titrated to sedation and succinylcholine titrated to muscle relaxation.

    Right unilateral ECT at 5-6x seizure threshold three times a week

    Interventions:
    • Other: IV Saline
    • Procedure: ECT
    • Drug: Muscle Relaxant
    • Drug: Anesthetic Agents
Publications * Not Provided

*   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 Terminated
Actual Enrollment  ICMJE
 (submitted: April 18, 2017)
17
Original Estimated Enrollment  ICMJE
 (submitted: December 14, 2010)
30
Actual Study Completion Date  ICMJE November 1, 2012
Actual Primary Completion Date October 26, 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. males and females between the ages of 18-65,
  2. DSM-IV diagnosis of Major Depressive Disorder (MDD), without psychotic features
  3. HAM-D-28 score of 20 or higher
  4. requiring ECT treatment as part of their psychiatric care Comorbid anxiety disorders (OCD, Generalized anxiety, panic disorder) will be allowed as long as the clinician administering the SCID believes that they are not the primary diagnosis.

Exclusion Criteria:

  1. MDD with a score of <20 on the HAM-D 28,
  2. Other DSM-IV primary diagnoses including major depressive disorder with psychotic features, bipolar disorder, schizoaffective disorder, schizophrenia, dementia
  3. any history of psychosis
  4. substance use disorder (abuse or dependence with active use within the last 6 months), and any lifetime history of ketamine abuse or dependence;
  5. organic mental disorders;
  6. seizure disorder or chronic antiepileptic medications;
  7. severe or unstable medical illness, including history of closed head injury resulting in loss of consciousness, medical contraindication to anesthesia or to ECT (i.e. recent myocardial infarction, increased intracranial pressure)
  8. current treatment with memantine
  9. pregnancy, or females of reproductive age who are not using an accepted method of contraception (birth control pill, IUD, combination of barrier methods).
  10. known hypersensitivity to ketamine
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01260649
Other Study ID Numbers  ICMJE 2010P001672
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Cristina Cusin, MD, Massachusetts General Hospital
Study Sponsor  ICMJE Massachusetts General Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Massachusetts General Hospital
Verification Date April 2017

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