Neural Circuit Effects of Ketamine in Depression

NCT ID: NCT06213324

Last Updated: 2025-07-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-01-31
• Study Completion Date: 2028-04-30

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 Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Ketamine

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

Group Type: EXPERIMENTAL

Ketamine

Intervention Type: DRUG

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

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Normal saline delivered intravenously

Interventions

Ketamine

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

Intervention Type: DRUG

Placebo

Normal saline delivered intravenously

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

James Murrough

Professor of Psychiatry and Neuroscience

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

James Murrough, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Laurel Morris

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sibilla Masieri

Role: CONTACT

sibilla.masieri@mssm.edu

Facility Contacts

Sibilla Masieri

Role: primary

Sibilla.Masieri@mssm.edu,

Other Identifiers

R01MH134045

Identifier Type: NIH

Identifier Source: secondary_id

View Link

GCO 22-1619

Identifier Type: -

Identifier Source: org_study_id