NCT06480201

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

• Status: Suspended
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 100 (estimated)
• Sponsor: Texas A&M University · Academic / Other
• Sex: All
• Age: 21 Years – 45 Years
• Healthy volunteers: Accepted

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.

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.

Conditions

• Healthy
• Major Depressive Disorder
• Treatment Resistant Depression

Interventions

Type	Name	Description
DRUG	Ketamine	Ketamine infusion amount is dictated by BMI, sex, and age.
OTHER	Saline	Saline infusion amount is dictated by BMI, sex, and age.

Timeline

• Start date: 2024-01-01
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2024-06-28
• Last updated: 2026-03-23

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study