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

NCT06480201 | Recruiting Phase 1 FDA Drug

• 1 other identifier: H-54099
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 2

Brief Summary

The core objective of this study is to enhance the translational potential of this electroencephalogram (EEG) biomarker by using ketamine(KET)-induced gamma potentiation as a prognostic marker of 4-week treatment outcome. Previous research focused exclusively on KET-induced gamma band potentiation (GBP) in the context of a single infusion. Our study design captures the clinical variation associated with real-world treatment resistant depression (TRD) patients and allows us to analyze the relative importance of GBP to antidepressant symptom reduction across the induction phase of treatment. If successful, it provides a compelling rationale for a larger prospective investigation of gamma dynamics as a moderator of outcome to varied TRD therapies which impact the balance of cortical excitation and inhibition.

Conditions

Healthy; Major Depressive Disorder; Treatment Resistant Depression

Keywords

depression; ketamine

Outcome Measures

Primary Outcomes (3)

• Resting State Gamma Power

  Gamma power is the resting state electroencephalogram represents the amplitude of oscillations measuring the in the 30+ hertz (Hz) range of the power-spectrum. This is used as a proxy measure of the level of cortical disinhibition occurring at rest.

  Before infusion, during infusion, 60-90 minutes after infusion

• Auditory Steady State Response Gamma Power

  Auditory Steady State Response gamma power represents the entrainment of inhibitory interneurons in response to a train of short tones, resembling a high frequency click, that are presented for a 1000ms at a rate of 40 Hz.

  Before infusion, during infusion, 60-90 minutes after infusion

• Montgomery-Asberg Depression Rating Scale (MADRS)

  The MADRS is a clinician administered rating scale consisting of 10 items to measure depression symptom severity. Each item has a rating scale of 0-6. Greater total scores indicate more severe depression.

  Study entry, pre-infusion, study exit visit (up to a month after infusion)

Secondary Outcomes (1)

• Quick Inventory of Depressive Severity Self Report (QIDS-SR)

  Study entry, pre-infusion, study exit visit (up to a month after infusion)

Study Arms (3)

Healthy Controls

ACTIVE COMPARATOR

Healthy controls will receive one saline and ketamine infusion.

Drug: Ketamine; Other: Saline

Major Depressive Disorder

ACTIVE COMPARATOR

Major Depressive Disorder participants will receive one saline and ketamine infusion.

Drug: Ketamine; Other: Saline

Treatment Resistant Depression

ACTIVE COMPARATOR

Treatment Resistant Depression participants will receive 8 ketamine infusions where their first and fourth infusions are a saline and ketamine infusion.

Drug: Ketamine; Other: Saline

Interventions

Ketamine DRUG

Ketamine infusion amount is dictated by BMI, sex, and age.

Healthy Controls; Major Depressive Disorder; Treatment Resistant Depression

Saline OTHER

Saline infusion amount is dictated by BMI, sex, and age.

Healthy Controls; Major Depressive Disorder; Treatment Resistant Depression

Eligibility Criteria

• Age: 21 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.
• Male or Female ages 21-45, inclusive.
• Level of understanding sufficient to agree to all tests and examinations required by the protocol.
• 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.
• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• Texas A&M University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (2)

Wells Medicine

Houston, Texas, 77024, United States

RECRUITING

Texas A&M (Houston Methodist Hospital Location)

Houston, Texas, 77030, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant; Depression

Interventions

Ketamine; Sodium Chloride

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Central Study Contacts

Julia Engelhardt

CONTACT

713-689-9856; julia.engelhardt@bcm.edu

Nicholas Murphy

CONTACT

713-798-7593; nicholas.murphy@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Infusion order of saline to ketamine is single blind.
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: This trial is designed to study the mechanics of KET induced gamma band potentiation (GBP) as they relate to antidepressant outcome following a KET induction course. Disease (major depressive disorder \[MDD\]) and healthy control groups are included to measure disease and medication specific effects on initial KET induced GBP. The KET-EEG visits (infusion #1 \[all groups\], infusion #4 \[TRD only\]) follow a fixed-order, single-blind placebo-controlled crossover design.

Study Record Dates

• First Submitted: June 19, 2024
• First Posted: June 28, 2024
• Study Start: January 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 6, 2026

Record last verified: 2026-01

Locations

US (2)