Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine (NCT06788249) | Clinical Trial Compass
RecruitingEarly Phase 1
Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine
United States10 participantsStarted 2026-04-01
Plain-language summary
In the treatment of Major Depressive Disorder (MDD), ketamine can produce rapid but short-lasting improvements in mood. In order to develop a new generation of treatments with rapid and sustained efficacy, a better understanding of the mechanism of action is urgently needed. One candidate mechanism is the modulation of synaptic strength mediated by glutamatergic activity as ketamine has been suggested to increase synaptic strength. Although determining how ketamine impacts the glutamatergic system is essential to isolating its mechanism of action, the invasive nature of most assessment methods has limited our ability to do so in humans. The proposed research aims to determine if changes in glutamatergic activity, reflecting the modulation of synaptic strength, underlie the antidepressant effects of ketamine. In this project, the investigators will utilize a novel measure of glutamate imaging, GluCEST, to assess changes in glutamatergic activity to assess synaptic strength following ketamine administration. Ten individuals (aged 25-65) with a DSM-V diagnosis of MDD will undergo baseline GluCEST imaging prior to and following ketamine infusion. Both clinician-administered and subjective mood measures will be collected. It is predicted that ketamine will improve mood and increase glutamatergic activity and synaptic strength. Results from this project have the potential to identify the modifiable mechanisms by which rapid antidepressants work which could ultimately stimulate the development of novel interventions that work through the modulation of glutamatergic activity.
Who can participate
Age range
25 Years – 65 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Age between 25 and 65 years;
. Current depression as assessed on the SCID;
. Treatment-resistant depression, as defined by failure of at least two previous antidepressant or mood stabilizing treatments within the current depressive episode. Failed antidepressant or mood stabilizing treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks
. Able to comprehend English, as all questionnaires are in this language
. Ability to provide informed consent Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.
Exclusion criteria
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1This trial is described as a pilot study in early Phase 1 — does that mean there's still a lot unknown about the safety profile of this particular ketamine protocol, and how does that affect whether it might be right for me?
2The study is measuring something called GluCEST imaging metrics, which sounds like it's focused on understanding how ketamine changes brain chemistry rather than directly treating my depression — can you help me understand whether participants might still get a real therapeutic benefit, or is this primarily a research study?
3Since ketamine can have dissociative or psychological side effects, what would the monitoring look like during and after the infusions in this trial, and how does that compare to how ketamine is managed in a standard clinical setting?
4Given that this is a pilot study still in early stages, would it make sense for me to try established treatments for my major depressive disorder first, or is there a reason this trial might be worth considering sooner in my treatment journey?
5Are there any specific requirements — like the type of brain imaging equipment involved or the number of visits — that could make participation logistically difficult, and what should I know about the time commitment before deciding whether to discuss this further with you?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
GluCEST imaging metrics
Timeframe: From pre to post-ketamine infusion (2 imaging sessions over a 9-hour span)
. A sleep disorder other than insomnia, as determined by history;
. History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia and other psychotic disorders as assessed on the SCID;
. Alcohol or drug abuse in the past year based upon the SCID or urine toxicology screen;
. A current smoker;
. Patients with a BMI over 40.
. Ongoing prescription of 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
. Currently undergoing ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;
. Use of any MAOI is prohibited two weeks prior to administration of study drug; if patients are on an MAOI when enrolled, study drug will not be administered until two weeks off MAOI;