Major Depressive DisorderPhase 4NCT06213324

Neural Circuit Effects of Ketamine in Depression

A Phase 4 study testing Ketamine in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 to 65 yearsHealthy volunteers can take part
Conditions the study is for: Major Depressive Disorder
What is being tested?: Ketamine
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 120 participants
Where: 1 siteUnited States
Study dates: 31 Jan 2024to 1 Feb 2028
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
Healthy volunteers accepted
Adult, Older adult

Who may be able to join

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;

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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;

Who cannot join

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);

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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.

Trial locations and contacts

1 site in 1 country.

United States1 site

Icahn School of Medicine at Mount Sinai
New York, New York, 10029

Other trials in United States

About this study

Official title: Neural Circuit-Specific Mechanisms of Ketamine's Effect on Anhedonia and Anxiety in Depression Using Ultra-High Field 7-Tesla MRI

Conditions: Major Depressive Disorder
Being tested: Ketamine, Placebo
Medical subject headings: Depressive Disorder, Major

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

Study groups in NCT06213324
Study group	Role	What they receive
Ketamine	Experimental	Participants in the ketamine arm will receive a single infusion of ketamine Receives: Drug: Ketamine
Placebo	Placebo comparator	Participants in the placebo arm will receive a single placebo infusion of normal saline Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

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.
Measured: Baseline

Secondary outcomes (1)

Treatment-related change in sgACC response to the Incentive Flanker Task
Treatment-related change from baseline to 1-day post treatment in 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. MDD adults only.
Measured: Baseline and Day 1

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

31 Jan 20241 Feb 2028

First posted19 Jan 2024
Study start31 Jan 2024
Primary completion1 Jan 2028 (estimated)
Study completion1 Feb 2028 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 120 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06213324
Sponsor's protocol ID: GCO 22-1619
Other IDs: R01MH134045
Status last verified: Nov 2026
First submitted: 9 Jan 2024
Last updated: 4 Nov 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: All of the individual participant data collected during the trial, after deidentification.

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Major Depressive Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 4 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Neural Circuit-Specific Mechanisms of Ketamine's Effect on Anhedonia and Anxiety in Depression Using Ultra-High Field 7-Tesla MRI
ClinicalTrials.gov ID: NCT06213324
Acronym / sponsor ID: GCO 22-1619
Conditions: Major Depressive Disorder
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 120 participants (actual)
Lead sponsor: Icahn School of Medicine at Mount SinaiUniversity, hospital or other
Collaborators: National Institute of Mental Health (NIMH)
Study start: 31 Jan 2024 (actual)
Primary completion: 1 Jan 2028 (estimated)
Study completion: 1 Feb 2028 (estimated)
First posted: 19 Jan 2024 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Ketamine	Experimental	Drug: KetamineParticipants in the ketamine arm will receive a single infusion of ketamine
Placebo	Placebo comparator	Drug: PlaceboParticipants in the placebo arm will receive a single placebo infusion of normal saline

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult

Key inclusion criteria (13 listed)

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);

Key exclusion criteria (24 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Ketamine0.5 mg/kg ketamine dissolved in 100 mL saline, delivered intravenously	Drug	Ketamine
PlaceboNormal saline delivered intravenously	Drug	Placebo

Primary outcome

sgACC response to the Incentive Flanker Task
Time frame: Baseline
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.

1 secondary outcome

Treatment-related change in sgACC response to the Incentive Flanker Task
Time frame: Baseline and Day 1

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2026.
Individual participant dataSharing planned: Yes. All of the individual participant data collected during the trial, after deidentification.

Related trials for Major Depressive Disorder

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Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

James Murrough, MD/PhD principal investigator

Icahn School of Medicine at Mount Sinai

Laurel Morris principal investigator

Icahn School of Medicine at Mount Sinai

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ketamine in people with Major Depressive Disorder, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 4 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

sgACC response to the Incentive Flanker Task (time frame: Baseline). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06213324.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2026.