Actively Recruiting
Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid Receptor Components of the Anti-Depressant Ketamine Response
Led by Yale University · Updated on 2026-05-06
50
Participants Needed
1
Research Sites
N/A
Total Duration
On this page
Sponsors
Y
Yale University
Lead Sponsor
N
National Institute of Mental Health (NIMH)
Collaborating Sponsor
AI-Summary
What this Trial Is About
Researchers are evaluating the combined effects of perampanel and ketamine on people with treatment-resistant depression. The study aims to test the idea that stimulating Alpha-Amino-3-Hydroxy-5-Methyl-4-Isoxazole Propionic Acid receptors (AMPAR) is important for ketamine's anti-depressant response. This is the first human study to explore whether blocking AMPAR affects ketamine's ability to reduce depression symptoms and influence brain activity. Participants will receive two treatments in a randomized, double-blind crossover design: ketamine combined with either oral perampanel (6 mg) or an oral placebo. Each treatment day includes a 2-hour MRI scan during ketamine infusion, followed by another scan and symptom assessments 24 hours later. The study includes a screening session to ensure safety for receiving these drugs. During the study, participants undergo physical exams, blood and urine tests, electrocardiograms, and drug and alcohol screenings. Researchers measure brain connectivity and oxygen metabolism during ketamine infusion and assess clinical improvement with depression rating scales 24 hours afterward. Safety monitoring continues throughout, and participants are advised not to drive or operate heavy machinery for 24 hours after infusion. The entire process involves two treatment days approximately 21 days apart.
CONDITIONS
Brief Title
Alpha-Amino-3-Hydroxy-5-Methyl-4- Isoxazole Propionic Acid Receptor Components of the Anti-Depressant Ketamine Response
Who Can Participate
Eligibility Criteria
You may qualify if you...
- Right-handed as determined by the Edinburgh Handedness Inventory
- Current depression with a score greater than 17 on the Hamilton Depression Rating Scale
- Antidepressant-resistant depressive symptoms with failure of one or more adequate antidepressant trials
- Previous positive response to ketamine treatment if previously received
- Meet DSM-5 criteria for major depressive disorder confirmed by SCID-5
- Engaged in treatment outside the research protocol (pharmacotherapy or psychotherapy) with stable treatment for at least 4 weeks
- Willing to refrain from caffeine, drug, and alcohol use for one week before each MRI session
- Females must not be pregnant or breastfeeding and agree to use medically accepted birth control methods or be surgically sterile or post-menopausal
- Able to read and write English
- Have at least a 12th grade education or equivalent
You will not qualify if you...
- Serious suicide risk as indicated by Columbia Suicide Severity Rating Scale or clinical judgment
- Neurological disorders other than migraine or more than mild head injury
- Current therapeutic treatment with ketamine
- Current use of topiramate, memantine, barbiturates, daytime benzodiazepines, or monoamine oxidase inhibitors within specified time frames
- Recent treatment with vagal nerve stimulator, ECT, or deep brain stimulation
- Psychosis except mood-congruent psychotic experiences during depression
- Poorly controlled diabetes
- Other major medical disorders unless cleared by a study physician
- History of violence unless cleared by investigators
- Recent substance or alcohol use disorder except mild alcohol use disorder at investigator discretion
- Positive urine drug or breathalyzer test
- Clinically significant ECG abnormalities
- Abnormal clinical chemistry or hematology unless cleared by study physician
- History of positive HIV or Hepatitis B
- Recent use of centrally active medicines or herbal supplements that interfere with the study
- Known sensitivity to ketamine or heparin
- Resting blood pressure or heart rate outside specified ranges unless cleared
- History of intellectual disability or claustrophobia
- Significant visual impairment or color vision deficiency
- Presence of pacemaker, electronic devices, or ferromagnetic metal in vulnerable positions
- Advised not to drive or operate heavy machinery for 24 hours after infusion
- Recent significant blood donation or loss
- Other exclusions at investigator discretion
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
Your Study Journey
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Duration - Approximately 1 day per treatment session with about 21 days between sessions
Participants receive oral perampanel or placebo followed by intravenous ketamine infusion during two separate treatment sessions approximately 21 days apart. Each session includes a 2-hour MRI scan during the ketamine infusion and assessments the following day.
2 treatment visits with MRI scans and 2 follow-up visits for symptom assessment (1 visit the following day after each treatment)
Trial Site Locations
Total: 1 location
1
Yale University
New Haven, Connecticut, United States, 06511
Actively Recruiting
Research Team
N
Naomi Driesen, Ph.D.
E
Elizabeth Traester, B.A.
How is the study designed?
Study Type
INTERVENTIONAL
Masking
DOUBLE
Allocation
RANDOMIZED
Model
CROSSOVER
Primary Purpose
BASIC_SCIENCE
Number of Arms
2
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