Neural Circuit Effects of Ketamine in Depression

NCT06213324 | Recruiting Phase 4 DMC FDA Drug

• 2 other identifiers: GCO 22-1619R01MH134045
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

This project is designed to examine the role of the subgenual anterior cingulate cortex (sgACC) in anhedonia and anxiety in humans with depression, as well as the acute and sustained effects of ketamine on agACC activation and depression symptoms.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• sgACC response to the Incentive Flanker Task

  Subgenual anterior cingulate cortex (sgACC) response to reward measured by the BOLD (Blood Oxygen Level Dependent) signal within the sgACC region of the brain, during an fMRI Incentive Flanker Task in healthy controls and in adults with MDD. BOLD signal is the unit of measure of this outcome.

  Baseline

Secondary Outcomes (1)

• Treatment-related change in sgACC response to the Incentive Flanker Task

  Baseline and Day 1

Study Arms (2)

Ketamine

EXPERIMENTAL

Participants in the ketamine arm will receive a single infusion of ketamine

Drug: Ketamine

Placebo

PLACEBO COMPARATOR

Participants in the placebo arm will receive a single placebo infusion of normal saline

Drug: Placebo

Interventions

Ketamine DRUG

0.5 mg/kg ketamine dissolved in 100 mL saline, delivered intravenously

Ketamine

Placebo DRUG

Normal saline delivered intravenously

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MDD Group
• Male or female aged 18-65 years;
• Ability for participant to comply with the requirements of the study as determined by the PI;
• Capacity to provide informed consent;
• Meets diagnostic criteria for current MDD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5);
• In a current major depressive episode (MDE) of at least moderate severity according to DSM-5;
• Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year).
• Women of childbearing potential must have a negative pregnancy test at screening and prior to the infusion.
• HC Group
• Male or female aged 18-65 years;
• Capacity to provide informed consent;
• Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year).
• Ability for participant to comply with the requirements of the study as determined by the PI;

You may not qualify if:

• MDD Group
• Current or history of schizophrenia or other psychotic disorder/episode, bipolar disorder, neurodevelopmental disorder, or neurocognitive disorder;
• Current major depressive disorder with psychotic features;
• Substance use disorder within the past 2 years\*;
• Lifetime history of ketamine use disorder;
• Antidepressant medication within 2 weeks of Baseline (4 weeks for fluoxetine);
• Severe current illness as reflected by a CGI score \>5;
• Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
• Clinically significant abnormalities of laboratories, physical examination, or ECG;
• Positive urine toxicology screen for drugs of abuse at the time of screening, except cannabis;
• Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
• Active suicidal intent or plan; CSSRS score \>2;
• Any contraindications to MRI, including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more;
• Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the participant or the quality of the data.
• HC Group

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• James Murrough, MD/PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

• Laurel Morris

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sibilla Masieri

CONTACT

sibilla.masieri@mssm.edu

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Psychiatry and Neuroscience

Study Record Dates

• First Submitted: January 9, 2024
• First Posted: January 19, 2024
• Study Start: January 31, 2024
• Primary Completion (Estimated): March 30, 2028
• Study Completion (Estimated): April 30, 2028
• Last Updated: July 3, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Immediately following publication. No end date.
• Access Criteria: Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. Any purpose. Specify Other Mechanism Data from this study will be submitted to the National Institute of Mental Health Data Archive (NDA). The NDA is a data repository run by the National Institute of Mental Health (NIMH) that facilitates data sharing across mental health and other research communities. Periodically during and after study completion, the researchers will upload deidentified data information to the NDA. Other researchers nationwide can then file an application to obtain access to deidentified study data for research purposes.

Locations

US (1)