Neural Circuit Effects of Ketamine in Depression

Major Depressive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06213324
• Other study ID #: GCO 22-1619
• Secondary ID: R01MH134045
• Status: Recruiting
• Phase: Phase 4
• Start date: January 31, 2024
• Est. completion date: April 30, 2028

Study information

• Verified date: February 2024
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Julia Berman
• Phone: 212-241-6539
• Email: julia.berman[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: April 30, 2028
• Est. primary completion date: March 30, 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Drug:
• Ketamine
0.5 mg/kg ketamine dissolved in 100 mL saline, delivered intravenously
• Placebo
Normal saline delivered intravenously

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Baseline and Day 1