Clinical trial NCT06213324: Neural Circuit Effects of Ketamine in Depression
Official title: Neural Circuit-Specific Mechanisms of Ketamine's Effect on Anhedonia and Anxiety in Depression Using Ultra-High Field 7-Tesla MRI
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Major Depressive Disorder
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2024-01-19
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


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.

Primary outcomes:
measure: sgACC response to the Incentive Flanker Task
timeFrame: Baseline
Secondary outcomes:
measure: Treatment-related change in sgACC response to the Incentive Flanker Task
timeFrame: Baseline and Day 1
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: James Murrough, MD/PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Icahn School of Medicine at Mount Sinai
name: Laurel Morris
role: PRINCIPAL_INVESTIGATOR
References: