Clinical TrialTreatment-Resistant Depression (TRD)KetaminePlaceboKetaminePlaceboKetaminePlaceboRecruiting

Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression

Phase I interventional study (n=100) using ketamine-induced gamma band potentiation (GBP) in healthy, MDD and TRD groups to prognose 4-week antidepressant outcome across an induction course.

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

Detailed Description

This study tests whether ketamine-induced EEG gamma band potentiation (GBP) predicts 4-week antidepressant outcome; healthy controls, MDD and TRD groups are included to dissociate disease and medication-specific effects.

Design uses fixed-order, single-blind saline-versus-ketamine crossover EEG assessments (infusion 1 for all groups; infusion 4 for TRD), and an eight-infusion induction course for TRD participants to capture real-world treatment variation.

Outcomes include GBP measures (>30 Hz) and clinical symptom change (MADRS) at 4 weeks; results will inform the translational utility of GBP as a prognostic biomarker for neuromodulatory therapies.

Study Protocol

Preparation

sessions

Dosing

8 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Healthy controls

active comparator

Healthy controls receive one saline and one ketamine infusion (fixed-order, single-blind crossover) to measure ketamine-induced gamma band potentiation.

Interventions

  • Ketamine
    via IV• single dose

    Ketamine infusion; dose dictated by BMI/sex/age per protocol.

  • Placebo
    via IV• single dose

    Saline infusion (placebo) for crossover EEG assessment.

MDD

active comparator

Major depressive disorder participants receive one saline and one ketamine infusion (fixed-order, single-blind crossover) for biomarker comparison.

Interventions

  • Ketamine
    via IV• single dose

    Ketamine infusion; dose dictated by BMI/sex/age per protocol.

  • Placebo
    via IV• single dose

    Saline infusion (placebo) for crossover EEG assessment.

TRD

active comparator

Treatment-resistant depression participants undergo an 8-infusion ketamine induction course with fixed-order saline vs ketamine crossover assessments at infusion 1 and infusion 4 (single-blind).

Interventions

  • Ketamine
    via IV• eight infusions• 8 doses total

    8-infusion induction course; ketamine dosing dictated by BMI/sex/age per protocol; EEG assessments include infusion 1 and infusion 4 crossover comparisons.

  • Placebo
    via IV• single dose

    Saline infusion (placebo) used in fixed-order crossover sessions (infusion 1 and/or infusion 4).

Participants

Ages
21 – 45
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. General
  • * The criteria for eligibility described here are intended to protect patient welfare where, for example, the administration of ketamine in the context of standardized research (i.e. pharmaco-EEG challenge) would be inadvisable or unsafe. An additional purpose is to decrease psychiatric co-morbidities that may affect the clinical phenomenology or treatment response and thus obscure findings. Further, by virtue of the eligibility criteria the investigators seek to limit variability due to demographic and other factors.
  • 2. All subjects Inclusion Criteria:
  • * Male or Female ages 21-45, inclusive.
  • * Level of understanding sufficient to agree to all tests and examinations required by the protocol.
  • 3. TRD patients
  • * Major depressive disorder (MDD) diagnosis confirmed by MINI, with major depressive episode of at least 4 weeks duration.
  • * MADRS score of 27 or greater.
  • * Meet criteria for treatment resistance, defined as 2+ unsuccessful trials of antidepressants at an adequate dose for at least 6 weeks.
  • * On a stable dose of all psychotropic medications (including antidepressant, antipsychotic, lithium, hypnotic, etc) for a minimum of 4 weeks prior to the Screening period.
  • 4. MDD patients
  • * MDD diagnosis confirmed by the Mini International Neuropsychiatric Interview (MINI), with major depressive episode of at least 4 weeks duration.
  • * MADRS score of less than or equal to 12.
  • * On a stable dose of all psychotropic medications (including antidepressant, antipsychotic, lithium, hypnotic, etc) for a minimum of 4 weeks prior to the Screening period.

Exclusion Criteria

  • Exclusion Criteria:
  • History of MDD with psychotic features, bipolar disorder, schizophrenia spectrum and other psychotic disorders, currently exhibiting psychotic features, or a first-degree relative with a psychotic disorder.
  • Diagnosed with intellectual disability.
  • Current major medical problems that affect brain anatomy, neurochemistry, or function, e.g., liver insufficiency, kidney insufficiency, cardiovascular problems, (unstable Arrhythmias, Chronic Heart Failure, Myocardial Infarction (MI) cardiac pacemaker), systemic infections, cancer, active upper respiratory infections, respiratory depression and any brain disorder (seizure disorder, stroke, dementia, degenerative neurologic diseases), and head injury with loss of consciousness for any period of time.
  • Pregnancy or Breast-feeding. All female participants in reproductive age will undergo pregnancy tests. Female participants will be required to provide evidence of use of contraceptives during the course of the study.
  • Unable to understand the design and requirements of the study.
  • Unable to sign the informed consent for any reason.
  • Patients with a severe personality disorder, including risk for homicide or aggressive behavior, which in the opinion of the investigator has a major impact on the patients' current psychiatric status and would preclude safe study participation.
  • Patients at serious and imminent risk of suicide and not suitable for an outpatient study, in the judgment of the investigators.
  • Patients taking medications with known activity at the N-methyl-D-aspartate (NMDA) or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor [eg, riluzole, amantadine, lamotrigine, memantine, topiramate, dextromethorphan, D-cycloserine], or the mu-opioid receptor.
  • Previous exposure to ketamine or esketamine.
  • Patients starting hormonal treatment (e.g., estrogen) in the 3 months prior to screening.
  • Patients with no regular contact with at least one adult. Patients who are un-domiciled are excluded.
  • Body mass index (BMI) >=40 kg/m2.
  • Active eating disorder or cognitive deficit affecting the regulation of food intake.
  • Current or recent course of electroconvulsive therapy (ECT) (past month).
  • History of deep brain stimulation (DBS), vagal nerve stimulation (VNS) implantation, or other form of psychosurgery
  • Recently started cognitive behavioral therapy (CBT) (past month).
  • Patients taking >6mg/day lorazepam (benzodiazepine)-equivalents. Patients with lower and/or infrequent use of benzodiazepines will be required to discontinue their dose on the morning (noting that this is already per protocol at the partner ketamine clinic).
  • Patients taking prescription opioids. Over the counter pain medications are proscribed on infusion days.
  • Dietary supplements affecting central nervous system (CNS) function will be discontinued before the study start. This will include supplementation of glutamate, serotonin (e.g. 5-hydroxytryptophan(HTP), St. John's Wort), creatine, γ-Aminobutyric acid (GABA).
  • Patients habitually consuming legal cannabis products containing cannabidiol (CBD) or delta-8-tetrahydrocannabinol (THC).
  • The participant has a known ketamine allergy or is taking any medication that may interact with ketamine.

Study Details

Locations

Wells Medicine — Houston, Texas, United States
Texas A&M (Houston Methodist Hospital Location) — Houston, Texas, United States

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