Using gamma oscillations to predict ketamine therapy outcomes in depression

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

This study is testing if brain activity measured during ketamine treatment can help predict how well it will work for people with depression that hasn't responded to other treatments.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Ages: 21 Years to 45 Years
• Sex: All
• Sponsor: Baylor College of Medicine (other)
• Locations: 2 sites (Houston, Texas and 1 other locations)
• Trial ID: NCT06480201 on ClinicalTrials.gov

What this trial studies

This study aims to investigate the use of gamma oscillations measured through electroencephalography (EEG) as a prognostic marker for treatment outcomes in patients with treatment-resistant depression (TRD) undergoing ketamine therapy. By analyzing the relationship between ketamine-induced gamma band potentiation and antidepressant symptom reduction, the study seeks to enhance the understanding of how neural circuitry responds to treatment. The research will involve administering ketamine and saline to participants while monitoring their EEG activity to assess the potential of gamma oscillations as a biomarker for predicting treatment efficacy.

Who should consider this trial

Good fit: Ideal candidates for this study are adults aged 21-45 with a confirmed diagnosis of major depressive disorder and a history of treatment resistance.

Not a fit: Patients with major depressive disorder who do not meet the criteria for treatment resistance or those outside the specified age range may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved prediction of treatment responses for patients with treatment-resistant depression, allowing for more personalized and effective therapeutic strategies.

How similar studies have performed: While the use of EEG biomarkers in predicting treatment outcomes is an emerging field, this specific approach focusing on gamma oscillations in the context of ketamine therapy is relatively novel.

Eligibility 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:

* 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 (AMPA) glutamate 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.

Where this trial is running

Houston, Texas and 1 other locations

• Wells Medicine — Houston, Texas, United States (RECRUITING)
• Baylor College of Medicine Jamail Specialty Care Center — Houston, Texas, United States (RECRUITING)

Study contacts

• Study coordinator: Julia Engelhardt

Conditions: Healthy, Major Depressive Disorder, Treatment Resistant Depression, depression, ketamine