Effects of Ketamine on Depression and Brain Activity

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

This study is testing whether ketamine can change brain activity and improve symptoms for people with major depressive disorder.

Quick facts

• Phase: Phase 4
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: Icahn School of Medicine at Mount Sinai (Academic / other)
• Locations: 1 site (New York, New York)
• Trial ID: NCT06213324 on ClinicalTrials.gov

What this trial studies

This project investigates how ketamine influences brain activity in the subgenual anterior cingulate cortex (sgACC) and its effects on symptoms of major depressive disorder (MDD). The study involves administering ketamine or a placebo to participants diagnosed with MDD to assess changes in brain activation and depression symptoms. By focusing on the sgACC, the research aims to deepen the understanding of the neural mechanisms underlying depression and the potential therapeutic effects of ketamine. Participants will be monitored for both immediate and sustained effects following treatment.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18-65 who are currently experiencing a major depressive episode of at least moderate severity.

Not a fit: Patients with mild depression or those not meeting the diagnostic criteria for major depressive disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for patients suffering from major depressive disorder.

How similar studies have performed: Other studies have shown promising results with ketamine in treating depression, indicating that this approach is supported by prior research.

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.

Where this trial is running

New York, New York

• Icahn School of Medicine at Mount Sinai — New York, New York, United States (Recruiting)

Study contacts

• Principal investigator: James Murrough, MD/PhD — Icahn School of Medicine at Mount Sinai
• Study coordinator: Sibilla Masieri

Conditions Major Depressive Disorder