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The Role of HNKs in the Antidepressant Effect of Ketamine

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ClinicalTrials.gov Identifier: NCT03977675
Recruitment Status : Terminated (PI left the institution)
First Posted : June 6, 2019
Last Update Posted : January 22, 2021
Sponsor:
Information provided by (Responsible Party):
Columbia University

Tracking Information
First Submitted Date  ICMJE June 5, 2019
First Posted Date  ICMJE June 6, 2019
Last Update Posted Date January 22, 2021
Actual Study Start Date  ICMJE May 15, 2019
Actual Primary Completion Date July 2, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 5, 2019)
  • Change in HNK Plasma Concentration [ Time Frame: Baseline and 80 minutes post-infusion ]
    HNK levels will be measured after ketamine administration.
  • Change in DHNK Plasma Concentration [ Time Frame: Baseline and 80 minutes post-infusion ]
    DHNK levels will be measured after ketamine administration.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE The Role of HNKs in the Antidepressant Effect of Ketamine
Official Title  ICMJE The Role of HNKs in the Antidepressant Effect of Ketamine
Brief Summary The objective of the proposed study is to examine the relationship between serum concentrations of HNK and changes in the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI), and the Profile of Mood States (POMS), as well as glutamatergic/GABAergic response. To achieve these aims the investigators propose a double-blind, uncontrolled (no placebo, no healthy control subjects) study with several different doses of ketamine. The investigators will conduct MRI scans to measure Glu and GABA before and during the ketamine treatment.
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.

Preliminary data support the rapid antidepressant benefit from ketamine but do not show a relationship between clinical improvement and the amount of ketamine, norketamine or dehydronorketamine (DHNK)(two of ketamine's metabolites) in the blood. The investigators hypothesize that a different metabolite of ketamine, hydroxynorketamine (HNK), produces the antidepressant effect of ketamine. The investigators have also 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 drug. 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Basic Science
Condition  ICMJE Major Depressive Disorder
Intervention  ICMJE Drug: Ketamine
Patients are assigned to one of three ketamine doses (0.3, 0.5, or 0.7 mg/kg) that will be administered intravenously.
Study Arms  ICMJE
  • Experimental: Ketamine 0.3 mg/kg
    Subjects are assigned to receive a dose of 0.3 mg/kg of Ketamine.
    Intervention: Drug: Ketamine
  • Experimental: Ketamine 0.5 mg/kg
    Subjects are assigned to receive a dose of 0.5 mg/kg of Ketamine.
    Intervention: Drug: Ketamine
  • Experimental: Ketamine 0.7 mg/kg
    Subjects are assigned to receive a dose of 0.7 mg/kg of Ketamine.
    Intervention: Drug: Ketamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: January 20, 2021)
8
Original Estimated Enrollment  ICMJE
 (submitted: June 5, 2019)
30
Actual Study Completion Date  ICMJE July 2, 2020
Actual Primary Completion Date July 2, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Current major depressive episode (MDE) as part of major depressive disorder (MDD). May be psychiatric medication-free or, if on psychiatric medications, not responding adequately.
  • Off all psychotropic and other types of drugs likely to interact with glutamate for at least 14 days before starting the study OR likely able to tolerate a medication washout.
  • Female subjects of child-bearing potential must be using an acceptable method of birth control throughout the study.

Exclusion Criteria:

  • 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.
  • Electroconvulsive therapy (ECT) within the last 3 months for current MDE.
  • Pregnancy or plans to conceive during the course of study participation.
  • Heart pacemaker, body implant or other metal in body.
  • Neurological disease or prior head trauma with evidence of cognitive impairment.
  • Claustrophobia sufficient to preclude MRI.
  • Prior ineffective trial of, or adverse effect to, ketamine.
  • IV drug use or history of ketamine use as a recreational drug ≥ 2 times or an adverse reaction to ketamine; any other drug or alcohol dependence within past 6 months.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03977675
Other Study ID Numbers  ICMJE NYSPI 7558
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Columbia University
Study Sponsor  ICMJE Columbia University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Michael Grunebaum, MD New York Psychiatric Institute
PRS Account Columbia University
Verification Date January 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP