NCT01700829

Brief Summary

This study is designed to compare the effectiveness of two medications, Ketamine and Midazolam, for rapidly relieving suicidal thoughts in people suffering from depression. The first drug, Ketamine, is an experimental antidepressant that early studies have shown may quickly reduce suicidal thoughts, but we are not sure how well it may work. Midazolam, the comparison drug, is not thought to reduce depression or suicidal thoughts.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
82

participants targeted

Target at P50-P75 for phase_4 major-depressive-disorder

Timeline
Completed

Started Jun 2012

Longer than P75 for phase_4 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

June 1, 2012

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

October 2, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 4, 2012

Completed
4.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 12, 2017

Completed
7 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 31, 2017

Completed
2.6 years until next milestone

Results Posted

Study results publicly available

March 11, 2020

Completed
Last Updated

March 11, 2020

Status Verified

March 1, 2020

Enrollment Period

4.6 years

First QC Date

October 2, 2012

Results QC Date

March 12, 2019

Last Update Submit

March 10, 2020

Conditions

Major Depressive DisorderSuicidal Ideation

Keywords

KetamineMidazolamMajor Depressive DisorderSuicidal ideationSuicideDepressionTreatmentKetamine Treatment

Outcome Measures

Primary Outcomes (1)

  • Change in Scale for Suicidal Ideation

    Change in suicidal ideation in depressed patients with moderate to severe suicidal thoughts from the pre-infusion baseline to 24 hours after the infusion with ketamine or midazolam, a sedative not known to reduce suicidal ideation, measured with Beck Scale for Suicidal Ideation - clinician rated version. This scale has 19 items scaled 0 (least severe) to 2 (most severe) and a potential score ranging from 0 to 38, with higher score indicating greater severity.

    Day 1 (24 hours) post-treatment

Secondary Outcomes (2)

  • Saliva Cortisol Awakening Response (CAR).

    Cort2 - Cort1 = (Day 1 30-mins post-awakening cortisol) - (Day 1 awakening cortisol)

  • Neuropsychological Effects

    Baseline and Day 1

Study Arms (2)

Midazolam

ACTIVE COMPARATOR

0.02 mg/kg, I.V. (in the vein)

Drug: Midazolam

Ketamine

ACTIVE COMPARATOR

0.5 mg/kg, I.V. (in the vein)

Drug: Ketamine

Interventions

KetamineDRUG

Single dose of 0.5 mg/kg of ketamine given intravenously (in the vein) over 40 minutes

Also known as: Ketalar, Ketamine Hydrochloride Injection
Ketamine
MidazolamDRUG

Single dose of 0.02 mg/kg of Midazolam given intravenously (in the vein) over 40 minutes

Also known as: Midazolam Injection
Midazolam

Eligibility Criteria

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

You may qualify if:

  • Unipolar depression with current major depressive episode (MDE). Participants may be psychiatric medication-free, or if on psychiatric medication, not responding adequately given current MDE with suicidal ideation (See 2).
  • Moderate to severe suicidal ideation
  • years old
  • Participants must agree to a voluntary admission to an inpatient research unit at the New York State Psychiatric Institute (NYSPI)for the infusion(s), for a brief stay, or longer if clinically necessary.
  • Pre-menopausal female participants of child-bearing potential must be willing to use an acceptable form of birth control during study participation such as condoms, diaphragm, or oral contraceptive pills.
  • Able to provide informed consent
  • Participants 61-65 years old must score a 25 or higher on the Mini-Mental State Examination (MMSE) at screening.

You may not qualify if:

  • Unstable medical condition or neurological illness, including baseline hypertension (BP\>140/90) or significant history of cardiovascular illness.
  • Significant ECG abnormality
  • Pregnant or lactating
  • Diagnosis of bipolar disorder or psychotic disorder
  • Contraindication to any study treatment.
  • Inadequate understanding of English.
  • Prior ineffective trial of or adverse reaction to Ketamine or Midazolam.
  • Opiate use greater than total daily dose of 20mg Oxycodone or equivalent during the 3 days pre-infusion.
  • A diagnosis of sleep apnea.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Columbia University/New York State Psychiatric Institute

New York, New York, 10032, United States

Location

Related Publications (4)

  • Hochschild A, Keilp JG, Madden SP, Burke AK, Mann JJ, Grunebaum MF. Ketamine vs midazolam: Mood improvement reduces suicidal ideation in depression. J Affect Disord. 2022 Mar 1;300:10-16. doi: 10.1016/j.jad.2021.12.055. Epub 2021 Dec 22.

    PMID: 34953926DERIVED

  • Keilp JG, Madden SP, Marver JE, Frawley A, Burke AK, Herzallah MM, Gluck M, Mann JJ, Grunebaum MF. Effects of Ketamine Versus Midazolam on Neurocognition at 24 Hours in Depressed Patients With Suicidal Ideation. J Clin Psychiatry. 2021 Nov 2;82(6):21m13921. doi: 10.4088/JCP.21m13921.

    PMID: 34727422DERIVED

  • Grunebaum MF, Mann JJ, Galfalvy HC, Gibbons RD. Computerized-Adaptive vs. Traditional Ratings of Depression and Suicidal Thoughts: An Assay Sensitivity Pilot Study in a Ketamine Clinical Trial. Front Psychiatry. 2021 Apr 7;12:602976. doi: 10.3389/fpsyt.2021.602976. eCollection 2021.

    PMID: 33897480DERIVED

  • Grunebaum MF, Galfalvy HC, Choo TH, Keilp JG, Moitra VK, Parris MS, Marver JE, Burke AK, Milak MS, Sublette ME, Oquendo MA, Mann JJ. Ketamine for Rapid Reduction of Suicidal Thoughts in Major Depression: A Midazolam-Controlled Randomized Clinical Trial. Am J Psychiatry. 2018 Apr 1;175(4):327-335. doi: 10.1176/appi.ajp.2017.17060647. Epub 2017 Dec 5.

    PMID: 29202655DERIVED

Related Links

MeSH Terms

Conditions

Depressive Disorder, MajorSuicidal IdeationSuicideDepression

Interventions

KetamineMidazolam

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental DisordersSelf-Injurious BehaviorBehavioral SymptomsBehavior

Intervention Hierarchy (Ancestors)

CyclohexanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsBenzodiazepinesBenzazepinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Results Point of Contact

Title
Michael Grunebaum, MD
Organization
NY State Psychiatric Institute-Columbia University Medical Center
michael.grunebaum@nyspi.columbia.edu
646-774-7573

Study Officials

  • Michael F. Grunebaum, M.D.

    Columbia University/New York State Psychiatric Institute

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Clinical Psychiatry

Study Record Dates

First Submitted

October 2, 2012

First Posted

October 4, 2012

Study Start

June 1, 2012

Primary Completion

January 12, 2017

Study Completion

July 31, 2017

Last Updated

March 11, 2020

Results First Posted

March 11, 2020

Record last verified: 2020-03

Locations

US(1)