Overview

This trial is active, not recruiting.

Condition major depressive disorder
Treatments ketamine, saline
Phase phase 2
Sponsor Columbia University
Collaborator National Institute of Mental Health (NIMH)
Start date February 2012
End date March 2016
Trial size 76 participants
Trial identifier NCT01558063, 6460

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, investigator, outcomes assessor)
Primary purpose treatment
Arm
(Active Comparator)
0.1 mg/kg, IV (in the vein)
ketamine
Single dose of 0.1 mg/kg of ketamine given intravenously over 40 minutes
(Active Comparator)
0.2 mg/kg, IV (in the vein)
ketamine
Single dose of 0.2 mg/kg of ketamine given intravenously over 40 minutes
(Active Comparator)
0.3 mg/kg, IV (in the vein)
ketamine
Single dose of 0.3 mg/kg of ketamine given intravenously over 40 minutes
(Active Comparator)
0.4 mg/kg, IV (in the vein)
ketamine
Single dose of 0.4 mg/kg of ketamine given intravenously over 40 minutes
(Active Comparator)
0.5 mg/kg, IV (in the vein)
ketamine
Single dose of 0.5 mg/kg of ketamine given intravenously over 40 minutes
(Placebo Comparator)
Saline infused over 40 minutes
saline
Single infusion of saline given intravenously over 40 minutes

Primary Outcomes

Measure
Ketamine Dose-Response Curve
time frame: Baseline and Day 1 (post ketamine)

Eligibility Criteria

Male or female participants from 18 years up to 65 years old.

INCLUSION CRITERIA: 1. Must be currently depressed EXCLUSION CRITERIA: 1. No history of other major psychiatric illnesses 2. No history of drug abuse

Additional Information

Official title The Antidepressant Action of Ketamine: Brain Chemistry
Principal investigator Matthew S. Milak, M.D.
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.
Trial information was received from ClinicalTrials.gov and was last updated in June 2015.
Information provided to ClinicalTrials.gov by Columbia University.