Clinical TrialMajor Depressive Disorder (MDD)KetamineNot yet recruiting

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

This open-label, early Phase I trial (n=10) will investigate the effects of a single intravenous ketamine infusion (0.5 mg/kg over 40 minutes) on glutamatergic activity and synaptic strength in individuals with treatment-resistant major depressive disorder (MDD).

Target Enrollment
10 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

This single-group, early-phase study will use GluCEST imaging at 7T to measure glutamatergic activity and inferred synaptic strength before and after a single intravenous ketamine infusion (0.5 mg/kg, 40 minutes) in people with treatment-resistant MDD.

Participants complete baseline clinical assessments (SCID, HAM-D, PANAS, VAS, POMS), a baseline MRI, the ketamine infusion with continuous vital monitoring, post-infusion mood assessments, a one-hour observation period, and a follow-up MRI later the same day to assess acute changes in glutamatergic signal.

Study Protocol

Preparation

sessions

Dosing

1 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Ketamine infusion

experimental

Single intravenous ketamine infusion (0.5 mg/kg over 40 minutes) in treatment-resistant MDD participants.

Interventions

  • Ketamine0.5 mg/kg
    via IV• single dose• 1 doses total

    40-minute infusion; monitored by nurse and anaesthesiologist.

Participants

Ages
25 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Age between 25 and 65 years;
  • 2. Current depression as assessed on the SCID;
  • 3. Treatment-resistant depression, defined by failure of at least two previous antidepressant or mood-stabilising treatments within the current depressive episode (adequate dose ≥8 weeks);
  • 4. Able to comprehend English;
  • 5. Ability to provide informed consent and pass a comprehension assessment related to ketamine and trial objectives.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. A sleep disorder other than insomnia;
  • 2. History of bipolar disorder, delirium, dementia, amnestic disorder, schizophrenia or other psychotic disorders as assessed on the SCID;
  • 3. Alcohol or drug abuse in the past year based on SCID or urine toxicology;
  • 4. Current smoker;
  • 5. Any significant medical or neurological illness that impacts brain function or impedes participation;
  • 6. History of head trauma with significant loss of consciousness;
  • 7. Metallic implants, pacemakers, tattoos, or other contraindications to MRI; claustrophobia or intolerance of scanner environment;
  • 8. Pregnancy;
  • 9. Untreated hypertension;
  • 10. BMI over 40;
  • 11. Ongoing prescription of ≥4 mg lorazepam equivalents daily, or morning dosing of any benzodiazepine at time of assessment;
  • 12. Current or recent ECT, transcranial magnetic stimulation, vagal nerve stimulation, or deep brain stimulation as acute or maintenance treatment;
  • 13. Use of any MAOI within two weeks prior to administration of study drug;
  • 14. Use of CYP3A4 inducers (carbamazepine, modafinil) within two weeks prior to administration and within 24 hours after last dose of study drug;
  • 15. Current use of naltrexone;
  • 16. Developmental delay or intellectual disability;
  • 17. Clinical or self-reported delirium, encephalopathy, or related diagnosis within the prior 12 months;
  • 18. Prior participation in another study of ketamine for depression;
  • 19. Prior treatment and/or recreational use of ketamine.

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment10 participants
  • Timeline
    Start: 2025-03-15
    End: 2026-04-15
  • Compound
    Ketamine
  • Topic
    Major Depressive Disorder (MDD)

Locations

United States

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