Clinical TrialMajor Depressive Disorder (MDD)KetamineNot yet recruiting

Integrating Ketamine Effects on Neuronal Molecular Signatures and the Brain Functional and Structural Connectome

Open-label, interventional mechanistic trial (n=120) using intravenous ketamine (0.5 mg/kg over 40 minutes, max 60 mg; three alternate-day infusions in MDD participants) to study molecular and connectome correlates of rapid antidepressant and anti-suicidal effects.

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

Detailed Description

This mechanistic clinical trial will evaluate molecular and imaging correlates of rapid antidepressant action of subanesthetic intravenous ketamine in patients with major depressive disorder.

Ninety depressed, medication-free participants will receive three alternate-day ketamine infusions (0.5 mg/kg over 40 minutes, maximum 60 mg) and be scanned at baseline and two post-treatment time points; thirty healthy controls will be scanned at two time points without treatment.

Outcomes include 7T structural, resting-state fMRI and DWI connectome measures, and molecular/gene expression profiles from olfactory-epithelium-derived neurons; mediation analyses will link molecular changes to connectome alterations and clinical improvement.

Study Protocol

Preparation

sessions

Dosing

3 sessions
40 min each

Integration

sessions

Study Arms & Interventions

Intravenous Ketamine

experimental

Intravenous ketamine 0.5 mg/kg over 40 minutes (max 60 mg); depressed participants receive three alternate-day infusions; healthy controls scanned without treatment.

Interventions

  • Ketamine0.5 mg/kg
    via IV• three infusions• 3 doses total

    0.5 mg/kg over 40 minutes; maximum 60 mg; 3 alternate-day treatments for MDD group

Participants

Ages
18 – 50
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Able to give voluntary informed consent.
  • 2. Meet DSM-5 criteria for Major Depressive Disorder (MDD) and currently in a Major Depressive Episode (MDE).
  • 3. Montgomery–Åsberg Depression Rating Scale (MADRS) score >21 and <32 (moderate to severe depression).
  • 4. Psychotropic medication-free for >2 weeks (or >5 weeks if on fluoxetine).
  • 5. Eligible for MRI per screening questionnaire.
  • 6. Clinically manageable as outpatient (CGI-S <5) with no suicidal/homicidal intent or behaviour.
  • 7. No contraindication to ketamine (e.g., allergy, uncontrolled hypertension).

Exclusion Criteria

  • Exclusion Criteria:
  • 1. DSM-5 diagnosis of (hypo)mania, bipolar disorder, schizophrenia, schizophreniform disorder, schizoaffective disorder, intellectual disability, or pervasive developmental disorder.
  • 2. Electroconvulsive therapy within the past 1 year.
  • 3. Moderate or severe substance or alcohol use disorder in the past 6 months (excluding caffeine or nicotine); evaluated by interview and urine toxicology.
  • 4. Serious medical or neurological illness, including known HIV positive status.
  • 5. Current pregnancy or breastfeeding.
  • 6. Contraindication to MRI (e.g., metallic implants).

Study Details

  • Status
    Not yet recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment120 participants
  • Timeline
    Start: 2025-01-01
    End: 2030-06-30
  • Compound
    Ketamine
  • Topic
    Major Depressive Disorder (MDD)

Locations

Massachusetts General Hosipital — Boston, Massachusetts, United States

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