Major Depressive DisorderEarly Phase 1NCT05327699
Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine
A Early Phase 1 study testing Ketamine in people with Major Depressive Disorder, run by Emory University at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Nov 2022to 2 Mar 2028
- Phase
- Early Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- Healthy Controls:
- willing and able to give written informed consent
- men or women, 18-65 years of age
Who cannot join
- 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)
Show all 28Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Emory University
Atlanta, Georgia, 30322
Michael Treadway, PhD, (404) 727-7541, ketaminestudy@emory.edu
Michael Treadway, PhD
About this study
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).
Read the detailed description
The main purpose of this study is to understand the effects of sub-anesthetic ketamine doses on varying functional domains of depression such as anhedonia, decision-making, and emotion processing in subjects diagnosed with Major Depressive Disorder (MDD). The study will evaluate these effects using a combination of questionnaires, neuroimaging techniques, and behavioral tasks. The clinical trial portion will only include subjects with MDD (Major Depressive Disorder). A separate group of healthy controls, n=60, will be invited to only complete a behavioral/interview session and one neuroimaging session.The healthy controls group will not be randomized nor receive any study intervention and will only serve to collect performance baseline measures. The primary aims of this study are to evaluate 1) the glutamate stress response in MDD patients and matched controls by whole-brain imaging, 2) the multi-modal associations between glutamate stress response and neuroimaging and behavioral assessments of motivation and valuation, and 3) the effect of ketamine versus placebo on glutamate stress response in MDD subjects.
- Conditions
- Major Depressive Disorder
- Being tested
- Ketamine, Placebo
- Keywords
- Neuroscience, Stress response
- Medical subject headings
- Depressive Disorder, Major, Fractures, Stress
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
A single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period.
PlaceboOther
A single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period.
| Study group | Role | What they receive |
|---|---|---|
| Major depressive disorder (MDD) Ketamine | Experimental | 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. Receives: Drug: Ketamine |
| Major depressive disorder (MDD) Placebo | Placebo comparator | Participants randomized to the placebo arm will receive a single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period. Receives: Other: Placebo |
| Healthy Controls | No intervention | The subjects in this group will not receive any intervention. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in glutamate concentration in the medial prefrontal cortex (mPFC)
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.
Measured: Baseline, 24 hours post-infusion, 14 days post-infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2022
- Study start8 Nov 2022
- Primary completion2 Mar 2028 (estimated)
- Study completion2 Mar 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Emory UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael Treadway, Emory University
- Investigators
- Michael Treadway, PhD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05327699
- Sponsor's protocol ID
- STUDY00003476
- Other IDs
- R01MH126083-01A1
- Status last verified
- May 2026
- First submitted
- 7 Apr 2022
- Last updated
- 26 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All members of this research team are strongly committed to open access data policies and the dissemination of research results in a timely manner. The results of the study will be published in a timely manner in the most appropriate journals and presented at relevant national and international conferences. Data will include participant data that underlie the results reported in a given article, after deidentification. No other documents will be included.
Study at a glance
From the registry record, last updated by the sponsor on 26 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glutamatergic Adaptation to Stress as a Mechanism for Anhedonia and Treatment Response With Ketamine
- ClinicalTrials.gov ID
- NCT05327699
- Acronym / sponsor ID
- STUDY00003476
- Conditions
- Major Depressive Disorder
- Keywords
- Neuroscience, Stress response
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 8 Nov 2022 (actual)
- Primary completion
- 2 Mar 2028 (estimated)
- Study completion
- 2 Mar 2028 (estimated)
- First posted
- 14 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
The main purpose of this study is to understand the effects of sub-anesthetic ketamine doses on varying functional domains of depression such as anhedonia, decision-making, and emotion processing in subjects diagnosed with Major Depressive Disorder (MDD). The study will evaluate these effects using a combination of questionnaires, neuroimaging techniques, and behavioral tasks. The clinical trial portion will only include subjects with MDD (Major Depressive Disorder). A separate group of healthy controls, n=60, will be invited to only complete a behavioral/interview session and one neuroimaging session.The healthy controls group will not be randomized nor receive any study intervention and will only serve to collect performance baseline measures. The primary aims of this study are to evaluate 1) the glutamate stress response in MDD patients and matched controls by whole-brain imaging, 2) the multi-modal associations between glutamate stress response and neuroimaging and behavioral assessments of motivation and valuation, and 3) the effect of ketamine versus placebo on glutamate stress response in MDD subjects.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Major depressive disorder (MDD) Ketamine | Experimental | Drug: KetamineParticipants 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. |
| Major depressive disorder (MDD) Placebo | Placebo comparator | Other: PlaceboParticipants randomized to the placebo arm will receive a single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period. |
| Healthy Controls | No intervention | –The subjects in this group will not receive any intervention. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (28 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: KetalarA single intravenous (IV) infusion of ketamine calculated at 0.5mg/kg through an indwelling catheter over a 40-100min period. | Drug | Major depressive disorder (MDD) Ketamine |
| PlaceboA single intravenous (IV) infusion of saline through an indwelling catheter over a 40-100min period. | Other | Major depressive disorder (MDD) Placebo |
Primary outcome
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.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 May 2026.
- Individual participant dataSharing planned: Yes. All members of this research team are strongly committed to open access data policies and the dissemination of research results in a timely manner. The results of the study will be published in a timely manner in the most appropriate journals and presented at relevant national and international conferences. Data will include participant data that underlie the results reported in a given article, after deidentification. No other documents will be included.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michael Treadway, PhD principal investigator
Emory University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Ketamine in people with Major Depressive Disorder, run by Emory University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 26 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Treadway, PhD ((404) 727-7541, ketaminestudy@emory.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in glutamate concentration in the medial prefrontal cortex (mPFC) (time frame: Baseline, 24 hours post-infusion, 14 days post-infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 May 2026.