Recruiting

Early Phase 1

KetamineGlutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine

Sponsor:

Emory University

Code:

NCT05327699

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Ketamine

Placebo

Study Details

Brief summary:

The main purpose of this study is to investigate the effects of ketamine on decision-making and emotion processing in a sample of individuals diagnosed with Major Depressive Disorder (MDD).

Conditions

Major Depressive Disorder

Study ID

NCT05327699

Start date

Nov 8, 2022

Status verified date

May, 2026

Completion date

Mar 2, 2028

Anticipated

Primary completion date

Mar 2, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Inclusion Criteria:

MDD Patients:

willing and able to give written informed consent
men or women, 18-65 years of age
primary diagnosis of DSM-V MDD, current, as diagnosed by the SCID-I
score of ≥20 on the Beck Depression Inventory, which will include patients characterized as having "moderate/severe" (20-28) or "very-severe" (29-63) depressive symptoms
off all antidepressant therapy for at least 8 weeks prior to the baseline visit

Healthy Controls:

willing and able to give written informed consent
men or women, 18-65 years of age

Exclusion Criteria:

MDD Patients:

history of any bipolar disorder or psychotic disorder
active psychotic symptoms of any type
substance abuse/dependence within 6 months of study entry (as determined by SCID)
unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination and laboratory testing), including upper respiratory disease or asthma, glaucoma or porphyria.
active suicidal ideation as determined by a score ≥3 on the Columbia Suicide Severity Rating Scale (C-SSR)
use of any recreational drugs as confirmed by urine drug screen at the time of scanning
pregnancy or lactation
use of glucocorticoids at any time during the study
Raynaud's disease that may interfere with the cold-pressor
contraindications for MRI
MMSE score <28
elevated blood pressure prior to infusion (systolic > 160 or diastolic >100)
history of treatment resistance as determined by ATRQ
prior adverse reaction to ketamine
use of antipsychotic medications
use of greater than 2mg daily of lorazepam or similar benzodiazipine.
Regular smoker as self-reported

Healthy Controls:

evidence of any psychiatric disorder with exception of specific phobia, and no history of any psychiatric disorder except mild past substance use disorder as diagnosed by the SCID-I
history of any substance abuse within the last 6 months
use of any recreational drugs as confirmed by urine drug screen at the time of scanning
pregnancy or lactation
use of glucocorticoids at any time during the study
Raynaud's disease that may interfere with the cold-pressor
contraindications for MRI
MMSE score <28
Regular smoker as self-reported

Study Design

Enrollment

140 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: Major depressive disorder (MDD) Ketamine

Participants randomized to the ketamine arm will receive a single intravenous (IV) infusion of ketamine at 0.5mg/kg through an indwelling catheter over a 40-100min period.

placebo comparator: Major depressive disorder (MDD) Placebo

Participants randomized to the placebo arm will receive a single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.

no intervention: Healthy Controls

The subjects in this group will not receive any intervention.

Interventions

Ketamine

A single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period.

Placebo

A single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.

Primary outcome measure

Change in glutamate concentration in the medial prefrontal cortex (mPFC) [ Time Frame: Baseline, 24 hours post-infusion, 14 days post-infusion ]

Central Contacts and Locations

Central contacts

Michael Treadway, PhD

(404) 727-7541 ketaminestudy@emory.edu

Locations

Emory University

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Michael Treadway, PhD

(404) 727-7541 ketaminestudy@emory.edu

Principal Investigator:

Michael Treadway, PhD

More Information

Sponsor

Emory University

Last update posted

May 26, 2026

Last verified

May, 2026

Keywords

Neuroscience
Stress response

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Emory University on 2026-05-26.