NCT05327699 · Emory University
Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine
What this study is about
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).
View original scientific description
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).
Interventions
DRUG
Ketamine
A single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period.
OTHER
Placebo
A single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.
Primary outcome measures
Change in glutamate concentration in the medial prefrontal cortex (mPFC)
Time frame: Baseline, 24 hours post-infusion, 14 days post-infusion
The glutamate concentration in the mPFC as determined by in vivo magnetic resonance spectroscopy (MRS) at a field strength of 3 Tesla (3T) using standard MRS protocols. The levels of glutamate metabolite will be quantified using a custom quantification algorithm for modelling the background noise inherent in NMR (Nuclear Magnetic Resonance) signals. In MDD participants receiving ketamine, acute stress challenges will result in decreased glutamate in mPFC at 24 hrs that will be sustained at 2 weeks.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Atlanta, Georgia
Collaborators
National Institute of Mental Health (NIMH)
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 26, 2026 · Source of record for eligibility and locations