Recruiting
Phase 4

Ketamine

Sponsor:

Icahn School of Medicine at Mount Sinai

Code:

NCT06213324

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Ketamine

Placebo

Study Details

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

Study ID

NCT06213324

Start date

Jan 31, 2024

Status verified date

Jun, 2025

Completion date

Apr 30, 2028

Anticipated

Primary completion date

Mar 30, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Inclusion Criteria:

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;

Exclusion Criteria:

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

  • Current or history of any psychiatric, neurodevelopmental disorder, or neurocognitive disorder;
  • Substance use disorder within the past 2 years\*;
  • 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 or physical examination;
  • Positive urine toxicology screen for drugs of abuse at the time of screening, except cannabis;
  • Current pregnancy;
  • Women who are breast feeding;
  • 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.

Study Design

Enrollment

120 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Ketamine

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

placebo comparator: Placebo

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

Interventions

Ketamine

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

Placebo

Normal saline delivered intravenously

Primary outcome measure

  • sgACC response to the Incentive Flanker Task [ Time Frame: Baseline ]

Central Contacts and Locations

Central contacts

Sibilla Masieri

sibilla.masieri@mssm.edu

Locations

Icahn School of Medicine at Mount Sinai

Recruiting

New York, New York, United States, 10029

Contacts

Sibilla Masieri

Sibilla.Masieri@mssm.edu,

Principal Investigator:

James Murrough, MD, PhD

More Information

Sponsor

Icahn School of Medicine at Mount Sinai

Last update posted

Jul 3, 2025

Last verified

Jun, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-16. This information was provided to ClinicalTrials.gov by Icahn School of Medicine at Mount Sinai on 2025-07-03. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.