Ketamine in the Treatment of Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2013 by Columbia University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Mate Milak, Columbia University
ClinicalTrials.gov Identifier:
NCT01558063
First received: March 16, 2012
Last updated: November 7, 2013
Last verified: November 2013
  Purpose

Depressed patients will be offered experimental treatment with a new, potentially fast-acting antidepressant called ketamine while being scanned by an MRI to measure the chemical effect of the drug. Ketamine will be given in a dose of 0.0 (placebo), 0.1, 0.2, 0.3, 0.4, or 0.5 mg/kg. If a patient does not respond to ketamine after the first infusion, it may be because s/he received ketamine placebo or the dose of ketamine was too low. In that case, an optional second scan and infusion of active ketamine (0.5 mg/kg) will be offered. This second scan will occur no later than weeks after the first scan/infusion (as scheduling permits). There is no guarantee that the patient will respond to the second ketamine infusion. Patients enrolled in the study are eligible for up to 6 months treatment with their study psychiatrist after the ketamine infusion(s). During this time, patients will be responsible for the cost of the conventional antidepressants but all doctors' visits will be free of charge. Healthy Volunteers: Healthy controls will receive an infusion of ketamine at a single dose (0.5 mg/kg). Volunteers will only receive one MRI scan and infusion.


Condition Intervention Phase
Major Depressive Disorder
Drug: Ketamine
Drug: Saline
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: The Antidepressant Action of Ketamine: Brain Chemistry

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • Ketamine Dose-Response Curve [ Time Frame: Baseline and Day 1 (post ketamine) ] [ Designated as safety issue: No ]
    The primary outcome is the dose-response curve as it refers to ketamine inducing a dose-dependent reduction in the 24-item Hamilton Depression Rating Scale (HDRS-24) scores of patients with major depressive disorder.


Estimated Enrollment: 76
Study Start Date: February 2012
Estimated Study Completion Date: November 2016
Estimated Primary Completion Date: November 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ketamine Dose 1
0.1 mg/kg, IV (in the vein)
Drug: Ketamine
Single dose of 0.1 mg/kg of ketamine given intravenously over 40 minutes
Active Comparator: Ketamine Dose 2
0.2 mg/kg, IV (in the vein)
Drug: Ketamine
Single dose of 0.2 mg/kg of ketamine given intravenously over 40 minutes
Active Comparator: Ketamine Dose 3
0.3 mg/kg, IV (in the vein)
Drug: Ketamine
Single dose of 0.3 mg/kg of ketamine given intravenously over 40 minutes
Active Comparator: Ketamine Dose 4
0.4 mg/kg, IV (in the vein)
Drug: Ketamine
Single dose of 0.4 mg/kg of ketamine given intravenously over 40 minutes
Active Comparator: Ketamine Dose 5
0.5 mg/kg, IV (in the vein)
Drug: Ketamine
Single dose of 0.5 mg/kg of ketamine given intravenously over 40 minutes
Placebo Comparator: Saline Solution
Saline infused over 40 minutes
Drug: Saline
Single infusion of saline given intravenously over 40 minutes

Detailed Description:

Major depressive disorder (MDD) is a common illness, affecting over 14 million American adults each year. MDD is a leading cause of disability worldwide, and is responsible for huge workplace and healthcare costs. The several week delay between onset of treatment and improvement in MDD symptoms with currently available treatments further increases the burden of the disorder. Shortening this delay is a major unmet challenge in the treatment of MDD. Studies report that a single intravenous low dose of a drug called ketamine can bring about substantial improvement in depression in hours, even in patients that have not improved with other antidepressant treatments. Certain aspects of ketamine's drug action are fairly well understood, but the question remains of how these properties relate to antidepressant effect. Our preliminary data support the rapid antidepressant benefit from ketamine. The investigators have used a scanner to measure the effects of ketamine on two major brain chemical transmitters and found that it causes a significant increase (more than 60%) in glutamate (Glu) and gamma aminobutyric acid (GABA) levels in the front of the brain. The investigators hypothesize that this increase in Glu and GABA levels, is responsible for the antidepressant action of the medication. Knowing how ketamine works could help to develop better medications that can be used orally and used for maintenance of the improvement seen with ketamine. The objective of the proposed dose finding study is to examine the relationship between the ketamine-induced improvement of MDD and the Glu and GABA responses to ketamine and to compare the Glu and GABA responses to ketamine in MDD and healthy subjects to better understand the pathophysiology of MDD. To achieve these aims this the investigators propose a randomized, placebo-controlled, double blind study with several different doses of ketamine. The investigators will conduct MRI scans to measure Glu and GABA before and during the ketamine treatment.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA:

1. Must be currently depressed

EXCLUSION CRITERIA:

  1. No history of other major psychiatric illnesses
  2. No history of drug abuse
  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: NCT01558063

Contacts
Contact: Shayna Friedman 6467745788 sf2654@columbia.edu

Locations
United States, New York
Columbia University/New York State Psychiatric Institute Recruiting
New York, New York, United States, 10032
Contact: Matthew S. Milak, M.D.         
Principal Investigator: Matthew S. Milak, M.D.         
Sponsors and Collaborators
Columbia University
Investigators
Principal Investigator: Matthew S. Milak, M.D. Columbia University
  More Information

Additional Information:
No publications provided

Responsible Party: Mate Milak, Assistant Professor of Clinical Psychology, Columbia University
ClinicalTrials.gov Identifier: NCT01558063     History of Changes
Other Study ID Numbers: 6460
Study First Received: March 16, 2012
Last Updated: November 7, 2013
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by Columbia University:
Ketamine
Major Depressive Disorder
Treatment
Depression

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

ClinicalTrials.gov processed this record on September 22, 2014