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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Massachusetts General Hospital
Sponsor:
Information provided by (Responsible Party):
Cristina Cusin, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT01260649
First received: December 7, 2010
Last updated: July 16, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Major Depressive Disorder
Drug: ketamine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • Hamilton Depression Rating scale - 28 [ Time Frame: one month ] [ Designated as safety issue: No ]
    HAMD will be administered at every ECT treatment, and 7-10 days after last ECT (approximately 1 month after baseline)


Secondary Outcome Measures:
  • cognitive side effects [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
    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 Autobiographic Memory Interview.


Estimated Enrollment: 30
Study Start Date: November 2010
Estimated Primary Completion Date: January 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
Drug: ketamine
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg), followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care
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

Drug: ketamine
eligible patients will be randomly assigned to a double-blind administration of ketamine (0.5 mg/kg), followed by the routine anesthetic agent and muscle relaxant. ECT will be administered as per standard of care

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01260649

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Cristina Cusin, MD    617-726-6421    ccusin@partners.org   
Contact: Charles Welch, MD    617-726-2990    cwelch1@partners.org   
Principal Investigator: Cristina Cusin, MD         
Sponsors and Collaborators
Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Cristina Cusin, MD, Instructor HMS, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT01260649     History of Changes
Other Study ID Numbers: 2010P001672
Study First Received: December 7, 2010
Last Updated: July 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Massachusetts General Hospital:
Electroconvulsive treatment
ketamine
Major Depression
Treatment-resistant Major Depressive Disorder

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Mood Disorders
Mental Disorders
Behavioral Symptoms
Anesthetics
Ketamine
N-Methylaspartate
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Excitatory Amino Acid Agonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Excitatory Amino Acid Antagonists

ClinicalTrials.gov processed this record on August 19, 2014