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Pilot Study: Establishing Glutamatergic Changes in Rapid Antidepressant Effects of Ketamine

NCT06788249 · Status: RECRUITING · Phase: EARLY_PHASE1 · Type: INTERVENTIONAL · Enrollment: 10

Last updated 2026-04-21

No results posted yet for this study

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.

Conditions

  • Major Depressive Disorder (MDD)

Interventions

DRUG

Ketamine only

The primary study intervention involves the administration of intravenous ketamine (0.5 mg/kg) over a 40-minute infusion. Ketamine, an NMDA receptor antagonist, has shown rapid antidepressant effects in individuals with treatment-resistant depression.

Sponsors & Collaborators

Principal Investigators

  • Jennifer R Goldschmied, PhD · University of Pennsylvania

Study Design

Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
25 Years
Max Age
65 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2026-04-01
Primary Completion
2026-08-15
Completion
2026-08-15
FDA Drug
Yes

Countries

  • United States

Study Locations

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Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT06788249 on ClinicalTrials.gov