NCT01558063

Brief Summary

Depressed patients will be offered experimental treatment with a new, potentially fast-acting antidepressant called ketamine while being scanned by magnetic resonance imaging (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). 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
38

participants targeted

Target at P25-P50 for phase_2 major-depressive-disorder

Timeline
Completed

Started Feb 2012

Longer than P75 for phase_2 major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2012

Completed
1 month until next milestone

First Submitted

Initial submission to the registry

March 16, 2012

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 20, 2012

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2015

Completed
4.2 years until next milestone

Results Posted

Study results publicly available

July 16, 2019

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2019

Completed
Last Updated

December 10, 2019

Status Verified

December 1, 2019

Enrollment Period

3.2 years

First QC Date

March 16, 2012

Results QC Date

April 11, 2019

Last Update Submit

December 3, 2019

Conditions

Major Depressive Disorder

Keywords

KetamineMajor Depressive DisorderTreatmentDepression

Outcome Measures

Primary Outcomes (1)

  • Number of Responders 24-hours Post-ketamine Infusion

    The quantitative depressive symptom ratings were collected at Baseline, Day 1 (post ketamine), Day 3 using HDRS-24 (a 24-item questionnaire used to provide an indication of depression, and as a guide to evaluate recovery). The total score can range from 0 to a maximum score of 15 with a higher score indicating a worse outcome. A "responder" was defined as an individual exhibiting a reduction in the HDRS score from baseline to 24 hours (day 1) post-treatment, and all other individuals were classified as non-responders.

    Day 1 (post ketamine)

Secondary Outcomes (2)

  • Change in Glutamate Levels

    Baseline and 120 minutes after infusion

  • Change in Gamma-Amino Butyric Acid (GABA) Levels

    Baseline and 120 minutes after infusion

Study Arms (6)

Ketamine Dose 1

ACTIVE COMPARATOR

0.1 mg/kg, IV (in the vein) of Ketamine and MRI scan

Drug: KetamineProcedure: Magnetic Resonance Imaging (MRI)

Ketamine Dose 2

ACTIVE COMPARATOR

0.2 mg/kg, IV (in the vein) of Ketamine and MRI scan

Drug: KetamineProcedure: Magnetic Resonance Imaging (MRI)

Ketamine Dose 3

ACTIVE COMPARATOR

0.3 mg/kg, IV (in the vein) of Ketamine and MRI scan

Drug: KetamineProcedure: Magnetic Resonance Imaging (MRI)

Ketamine Dose 4

ACTIVE COMPARATOR

0.4 mg/kg, IV (in the vein) of Ketamine and MRI scan

Drug: KetamineProcedure: Magnetic Resonance Imaging (MRI)

Ketamine Dose 5

ACTIVE COMPARATOR

0.5 mg/kg, IV (in the vein) of Ketamine and MRI scan

Drug: KetamineProcedure: Magnetic Resonance Imaging (MRI)

Saline Solution

PLACEBO COMPARATOR

Saline infused over 40 minutes and MRI scan

Drug: SalineProcedure: Magnetic Resonance Imaging (MRI)

Interventions

KetamineDRUG

Single dose of 0.1, 0.2, 0.3, 0.4 or 0.5 mg/kg of ketamine given intravenously over 40 minutes.

Also known as: Ketalar
Ketamine Dose 1Ketamine Dose 2Ketamine Dose 3Ketamine Dose 4Ketamine Dose 5
SalineDRUG

Single infusion of saline given intravenously over 40 minutes.

Also known as: Saline solution
Saline Solution
Magnetic Resonance Imaging (MRI)PROCEDURE

90-minute scan during the 40-minute infusion.

Ketamine Dose 1Ketamine Dose 2Ketamine Dose 3Ketamine Dose 4Ketamine Dose 5Saline Solution

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Patient suffering from a major depressive episode (MDE) as part of an major depressive disorder (MDD). Patients may be psychiatric medication-free or, if on psychiatric medications, not responding adequately.
  • Patient scores at least 22 on the Montgomery-Ã…sberg Depression Rating Scale (MADRS)
  • Age range 18-65 years
  • Patient is off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study with an exception of chloral hydrate or short acting benzodiazepines for distressing anxiety or insomnia
  • Subject is likely to be able to tolerate a medication washout
  • Female subjects of child-bearing potential must be using an acceptable method of birth control throughout the study.
  • Must be enrolled in New York Psychiatric Institute (NYSPI) study #4815

You may not qualify if:

  • Lifetime history of schizophrenia,schizoaffective illness, Bipolar Disorder, or psychosis.
  • First-degree relative with schizophrenia, schizoaffective disorder, or bipolar disorder if the subject is less than 33 years old
  • Significant uncontrolled physical illness particularly if it may affect the brain or glutamatergic system including blood dyscrasias lymphomas, hypersplenism, endocrinopathies, renal failure or severe chronic obstructive lung disease, autonomic neuropathies and active malignancy.
  • Subjects will be excluded for baseline hypertension (BP\>140/90) or significant history of cardiovascular illness
  • Significant ECG abnormalities
  • Lacks capacity to consent
  • Patients who are actively suicidal as defined by a suicidal ideation score of 4 or 5 or suicidal behavior score \> 0 on the Columbia Suicide Severity Rating Scale (C-SSRS) at in-person screening interview will be excluded from participating as outpatients and may only participate as inpatients if the independent inpatient treatment team agrees with the plan to enroll the patient.
  • Electroconvulsive therapy (ECT) within the last 3 months for this episode
  • Pregnancy or plans to conceive during the course of study participation
  • Heart pacemaker, body implant or other metal in body
  • A neurological disease or prior head trauma with evidence of cognitive impairment.
  • Patients who are responding satisfactorily to antidepressant medications because they will not be washed-out for purposes of this study
  • Claustrophobia sufficient to preclude MRI
  • Irremovable medicinal patch
  • Prior ineffective trial of, or adverse effect to, ketamine
  • +20 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (2)

  • Strong CE, Kabbaj M. Neural Mechanisms Underlying the Rewarding and Therapeutic Effects of Ketamine as a Treatment for Alcohol Use Disorder. Front Behav Neurosci. 2020 Dec 10;14:593860. doi: 10.3389/fnbeh.2020.593860. eCollection 2020.

    PMID: 33362485DERIVED

  • Milak MS, Rashid R, Dong Z, Kegeles LS, Grunebaum MF, Ogden RT, Lin X, Mulhern ST, Suckow RF, Cooper TB, Keilp JG, Mao X, Shungu DC, Mann JJ. Assessment of Relationship of Ketamine Dose With Magnetic Resonance Spectroscopy of Glx and GABA Responses in Adults With Major Depression: A Randomized Clinical Trial. JAMA Netw Open. 2020 Aug 3;3(8):e2013211. doi: 10.1001/jamanetworkopen.2020.13211.

    PMID: 32785636DERIVED

MeSH Terms

Conditions

Depressive Disorder, MajorDepression

Interventions

KetamineSodium ChlorideSaline SolutionMagnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsChloridesHydrochloric AcidChlorine CompoundsInorganic ChemicalsSodium CompoundsCrystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical PreparationsSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Results Point of Contact

Title
J. John Mann, MD
Organization
Columbia University
jjm@columbia.edu
646-774-7553

Study Officials

  • Michael F. Grunebaum, M.D.

    Columbia University

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 16, 2012

First Posted

March 20, 2012

Study Start

February 1, 2012

Primary Completion

May 1, 2015

Study Completion

October 1, 2019

Last Updated

December 10, 2019

Results First Posted

July 16, 2019

Record last verified: 2019-12

Data Sharing

IPD Sharing
Will not share

Locations

US(1)