Recruiting
Phase 1

Ketamine

Sponsor:

Texas A&M University

Code:

NCT06480201

Conditions

Healthy

Major Depressive Disorder

Treatment Resistant Depression

Eligibility Criteria

Sex: All

Age: 21 - 45

Healthy Volunteers: Accepted

Interventions

Ketamine

Saline

Study Details

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

Study ID

NCT06480201

Start date

Jan 1, 2024

Status verified date

Jan, 2026

Completion date

Dec 31, 2026

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 45

Healthy Volunteers: Accepted

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.

Study Design

Enrollment

100 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

active comparator: Healthy Controls

Healthy controls will receive one saline and ketamine infusion.

active comparator: Major Depressive Disorder

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

active comparator: Treatment Resistant Depression

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

Interventions

Ketamine

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

Saline

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

Primary outcome measure

  • Resting State Gamma Power [ Time Frame: Before infusion, during infusion, 60-90 minutes after infusion ]
  • Auditory Steady State Response Gamma Power [ Time Frame: Before infusion, during infusion, 60-90 minutes after infusion ]
  • Montgomery-Asberg Depression Rating Scale (MADRS) [ Time Frame: Study entry, pre-infusion, study exit visit (up to a month after infusion) ]

Central Contacts and Locations

Central contacts

Julia Engelhardt

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

Nicholas Murphy

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

Locations

Wells Medicine

Recruiting

Houston, Texas, United States, 77024

Contacts

Jesse Wells

(713) 589-5118mail@wellsmedicine.com

Texas A&M (Houston Methodist Hospital Location)

Recruiting

Houston, Texas, United States, 77030

Contacts

Nicholas Murphy

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

Sanjay Mathew

7137985877sjmathew@bcm.edu

More Information

Sponsor

Texas A&M University

Last update posted

Jul 6, 2026

Last verified

Jan, 2026

Keywords

  • depression
  • ketamine

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Texas A&M University on 2026-07-06.