- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03977675
The Role of HNKs in the Antidepressant Effect of Ketamine
Study Overview
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
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10032
- New York State Psychiatric Institute
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Ketamine 0.3 mg/kg
Subjects are assigned to receive a dose of 0.3 mg/kg of Ketamine.
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Patients are assigned to one of three ketamine doses (0.3, 0.5, or 0.7 mg/kg) that will be administered intravenously.
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Experimental: Ketamine 0.5 mg/kg
Subjects are assigned to receive a dose of 0.5 mg/kg of Ketamine.
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Patients are assigned to one of three ketamine doses (0.3, 0.5, or 0.7 mg/kg) that will be administered intravenously.
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Experimental: Ketamine 0.7 mg/kg
Subjects are assigned to receive a dose of 0.7 mg/kg of Ketamine.
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Patients are assigned to one of three ketamine doses (0.3, 0.5, or 0.7 mg/kg) that will be administered intravenously.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in HNK Plasma Concentration
Time Frame: Baseline and 80 minutes post-infusion
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HNK levels will be measured after ketamine administration.
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Baseline and 80 minutes post-infusion
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Change in DHNK Plasma Concentration
Time Frame: Baseline and 80 minutes post-infusion
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DHNK levels will be measured after ketamine administration.
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Baseline and 80 minutes post-infusion
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Michael Grunebaum, MD, New York Psychiatric Institute
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Mental Disorders
- Mood Disorders
- Depressive Disorder
- Depressive Disorder, Major
- Physiological Effects of Drugs
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Central Nervous System Depressants
- Peripheral Nervous System Agents
- Analgesics
- Sensory System Agents
- Anesthetics, Dissociative
- Anesthetics, Intravenous
- Anesthetics, General
- Anesthetics
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Ketamine
Other Study ID Numbers
- NYSPI 7558
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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