HealthyPhase 1NCT06480201
Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression
A Phase 1 study testing Ketamine and Saline in people with Healthy and Major Depressive Disorder, run by Texas A&M University at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy, Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Ketamine and Saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Jan 2024to 31 Dec 2026
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
- 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.
- TRD patients
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Wells Medicine
Houston, Texas, 77024
Jesse Wells, (713) 589-5118, mail@wellsmedicine.com
- Recruiting
Texas A&M (Houston Methodist Hospital Location)
Houston, Texas, 77030
Nicholas Murphy, 713-798-7593, nicholas.murphy@bcm.edu
Sanjay Mathew, 7137985877, sjmathew@bcm.edu
About this study
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.
Read the detailed description
Treatment-resistant depression (TRD) is a significant public health issue and the leading cause of disability in young and middle-aged adults. Treatment of depression via the rapid acting modulation of neural circuitry is at a critical stage of development with strategies such as ketamine (KET) infusion, esketamine nasal spray, and intermittent theta burst stimulation making substantial progress. Determining the prognosis for an intervention, however, remains a challenge due to the lack of a central biomarker to indicate the potential receptiveness of the target system (glutamate) to modulation. KET biomarker research has strong translational potential as a platform to enhance prognostic prediction of neuromodulatory therapeutics more broadly.
Electroencephalography (EEG) gamma band power is a neurophysiological measure of cortical excitability and synaptic potentiation. These processes are implicated in KET's mechanism as a N-methyl-D-aspartate (NMDA) receptor channel antagonist, making gamma power a candidate biomarker. In patients with TRD, the interaction between pre- and post-ketamine EEG gamma band amplitude (>30 Hz) has been identified as a biomarker for the optimal state of excitation/inhibition (E/I) balance required to achieve an antidepressant response from ketamine.
Theoretically, the process of gamma band potentiation (GBP) by ketamine represents the capacity of the brain to up-regulate glutamatergic activity in response to the initial infusion. In the context of the broader mechanism of action for ketamine treatment of depression GBP is likely tied to the integrity of downstream effects of ketamine. These processes regulate longer term patterns of cellular learning such as synaptic long-term potentiation, and therefore the efficiency with which they can be activated is a critical metric for understanding how likely patients will be to enter remission.
The core objective of this study is to enhance the translational potential of this EEG biomarker by using KET-induced gamma potentiation as a prognostic marker of 4-week treatment outcome. Previous research focused exclusively on KET-induced GBP in the context of a single infusion. Our study design captures the clinical variation associated with real-world 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.
- Being tested
- Ketamine, Saline
- Keywords
- depression, ketamine
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Ketamine infusion amount is dictated by BMI, sex, and age.
SalineOther
Saline infusion amount is dictated by BMI, sex, and age.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Controls | Active comparator | Healthy controls will receive one saline and ketamine infusion. Receives: Drug: Ketamine; Other: Saline |
| Major Depressive Disorder | Active comparator | Major Depressive Disorder participants will receive one saline and ketamine infusion. Receives: 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. Receives: Drug: Ketamine; Other: Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: 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)
The Quick Inventory of Depressive Severity Self Report is a 16 item measure of core behavioral domains associated with depression. These cover: sleep/wake cycles, affect, appetite, weight, concentration and decision making, self-perception, suicidality, general interest, and energy levels. Each item has a rating scale 0-3. Greater total scores indicate more severe depression
Measured: Study entry, pre-infusion, study exit visit (up to a month after infusion)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2024
- Study start1 Jan 2024
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Texas A&M University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Sanjay J. Mathew, MD, Texas A&M University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06480201
- Sponsor's protocol ID
- H-54099
- Status last verified
- Jan 2026
- First submitted
- 19 Jun 2024
- Last updated
- 15 Sep 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Gamma Oscillations as a Prognostic Marker for Ketamine Therapy in Treatment Resistant Depression
- ClinicalTrials.gov ID
- NCT06480201
- Acronym / sponsor ID
- H-54099
- Keywords
- depression, ketamine
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Texas A&M UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 28 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Treatment-resistant depression (TRD) is a significant public health issue and the leading cause of disability in young and middle-aged adults. Treatment of depression via the rapid acting modulation of neural circuitry is at a critical stage of development with strategies such as ketamine (KET) infusion, esketamine nasal spray, and intermittent theta burst stimulation making substantial progress. Determining the prognosis for an intervention, however, remains a challenge due to the lack of a central biomarker to indicate the potential receptiveness of the target system (glutamate) to modulation. KET biomarker research has strong translational potential as a platform to enhance prognostic prediction of neuromodulatory therapeutics more broadly.
Electroencephalography (EEG) gamma band power is a neurophysiological measure of cortical excitability and synaptic potentiation. These processes are implicated in KET's mechanism as a N-methyl-D-aspartate (NMDA) receptor channel antagonist, making gamma power a candidate biomarker. In patients with TRD, the interaction between pre- and post-ketamine EEG gamma band amplitude (>30 Hz) has been identified as a biomarker for the optimal state of excitation/inhibition (E/I) balance required to achieve an antidepressant response from ketamine.
Theoretically, the process of gamma band potentiation (GBP) by ketamine represents the capacity of the brain to up-regulate glutamatergic activity in response to the initial infusion. In the context of the broader mechanism of action for ketamine treatment of depression GBP is likely tied to the integrity of downstream effects of ketamine. These processes regulate longer term patterns of cellular learning such as synaptic long-term potentiation, and therefore the efficiency with which they can be activated is a critical metric for understanding how likely patients will be to enter remission.
The core objective of this study is to enhance the translational potential of this EEG biomarker by using KET-induced gamma potentiation as a prognostic marker of 4-week treatment outcome. Previous research focused exclusively on KET-induced GBP in the context of a single infusion. Our study design captures the clinical variation associated with real-world 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.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Healthy Controls | Active comparator | Drug: Ketamine, Other: SalineHealthy controls will receive one saline and ketamine infusion. |
| Major Depressive Disorder | Active comparator | Drug: Ketamine, Other: SalineMajor Depressive Disorder participants will receive one saline and ketamine infusion. |
| Treatment Resistant Depression | Active comparator | Drug: Ketamine, Other: SalineTreatment Resistant Depression participants will receive 8 ketamine infusions where their first and fourth infusions are a saline and ketamine infusion. |
Who may qualify
- Ages
- 21 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (14 listed)
- General
- All subjects Inclusion Criteria:
- TRD patients
- MDD patients
Key exclusion criteria (22 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineKetamine infusion amount is dictated by BMI, sex, and age. | Drug | Healthy Controls, Major Depressive Disorder, Treatment Resistant Depression |
| SalineSaline infusion amount is dictated by BMI, sex, and age. | Other | Healthy Controls, Major Depressive Disorder, Treatment Resistant Depression |
Primary outcome
Resting State Gamma Power
Time frame: Before infusion, during infusion, 60-90 minutes after infusion
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.
Auditory Steady State Response Gamma Power
Time frame: Before infusion, during infusion, 60-90 minutes after infusion
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.
Montgomery-Asberg Depression Rating Scale (MADRS)
Time frame: Study entry, pre-infusion, study exit visit (up to a month after infusion)
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.
1 secondary outcome
Quick Inventory of Depressive Severity Self Report (QIDS-SR)
Time frame: Study entry, pre-infusion, study exit visit (up to a month after infusion)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Ketamine and Saline in people with Healthy and Major Depressive Disorder, run by Texas A&M University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 15 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Julia Engelhardt (7136777595, epmadlab@tamu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting State Gamma Power (time frame: Before infusion, during infusion, 60-90 minutes after infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Sep 2026; AzTrials last refreshed its copy on 6 Nov 2026.