Clinical TrialMajor Depressive Disorder (MDD)KetaminePlaceboRecruiting

Neural Circuit Effects of Ketamine in Depression

This interventional trial (n=120) aims to explore the neural circuit-specific mechanisms of ketamine's effect on anhedonia and anxiety in individuals with major depressive disorder (MDD).

Target Enrollment
120 participants
Study Type
Phase IV interventional
Design
Randomized, quadruple Blind

Detailed Description

This study examines the role of the subgenual anterior cingulate cortex (sgACC) in anhedonia and anxiety in people with MDD and measures acute and sustained effects of a single IV ketamine infusion on sgACC activation and depressive symptoms.

Randomized, parallel-group design (ketamine versus saline placebo); outcomes include neuroimaging measures of sgACC activation, clinical ratings of anhedonia and anxiety, and safety/tolerability assessments.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Ketamine

experimental

Single intravenous infusion of ketamine (0.5 mg/kg) in MDD and HC groups.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

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

Placebo

inactive

Single intravenous normal saline infusion as placebo comparator.

Interventions

  • Placebo
    via IV• single dose• 1 doses total

    Normal saline infusion (100 mL) delivered intravenously.

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion 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

  • 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.

Study Details

Locations

Icahn School of Medicine at Mount Sinai — New York, New York, United States

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