Ketamine Associated ACC GABA and Glutamate Change and Depression Remission:

NCT03573349 | Active Not Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 17-011373
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a feasibility study and the goal of this project is to evaluate whether peak ACC GABA and glutamate, quantified as a CSF-corrected absolute concentration percent change from baseline, is associated with clinical remission, Montgomery Asberg Depression Rating Scale (MADRS) total score of \<10, to the anti-glutamatergic antidepressant ketamine. As MRS is expensive, we also aim to study a correlation between change in peripheral metabolites (GABA and glutamate) and central GABA and glutamate levels.

Conditions

Major Depressive Disorder; Treatment Resistant Depression; Bipolar Depression

Outcome Measures

Primary Outcomes (2)

• To evaluate percent change in the anterior cingulate cortex (ACC) GABA and Glutamate (baseline to peak) during a 40-minute IV ketamine infusion and remission (MADRS ≤9) at 24 hour

  Percent change in central metabolites and association with remission

  24 hour

• To evaluate a correlation between percent change in ACC GABA and Glutamate/Glx levels (baseline to peak) with a change in MADRS (baseline to 24 hours).

  Change in central metabolite and association with change in depression scores

  24 hour

Secondary Outcomes (2)

• To compare the percent change in peripheral GABA/Glutamate levels between remitters and non-remitters

  24 hour

• To evaluate the correlation between percent change in peripheral GABA and glutamate levels with a change in MADRS scores.

  24 hour

Study Arms (1)

Ketamine

OTHER

Open-label, non-randomized

Drug: Ketamine

Interventions

Ketamine DRUG

We will enroll 20 adults (aged 18-65 years) with treatment-resistant depression and will provide two i.v. ketamine infusions (0.5 mg/kg, infused over 40 minutes) and measure their depressive symptom responses. Biomarkers will be developed using blood samples from study subjects, taken prior to (predictive biomarkers), and following ketamine treatment (change biomarkers). This will be an open-label feasibility trial.

Ketamine

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent;
• Current psychiatric inpatient (voluntary only) or outpatient treatment;
• Male or female;
• Age 18-65 years;
• Meets diagnostic criteria for major depressive disorder/bipolar depression without psychotic features per the SCID DSM-IV-TR;
• PHQ-9 total score ≥ 15 at screening and at baseline (just prior to first acute phase ketamine infusion);
• Treatment-resistant depression (TRD), as defined by failure of at least two previous antidepressant treatments within the current depressive episode. Failed antidepressant treatments can include pharmacotherapy for depression at an adequate dose for at least 8 weeks, or an acute series of at least 6 administrations of electroconvulsive therapy (ECT) or an acute series of Transcranial magnetic stimulation (TMS);
• Ability to pass a comprehension assessment test related to effects of ketamine and trial objectives and criteria.

You may not qualify if:

• Inability to speak English
• Patients with a BMI \>40.
• Any current psychiatric diagnosis other than anxiety disorders needing concurrent antidepressant therapy
• Personality disorder being the primary diagnosis
• Diagnosis of schizophrenia, schizoaffective disorder, post-traumatic stress disorder, or active psychotic symptoms;
• Ongoing prescription of \> 4 mg lorazepam equivalents (total) daily, or morning dosing of any benzodiazepine at the time of assessment;
• Medications known to affect glutamate (i.e., riluzole, carbamazepine) or GABA (zaleplon, zolpidem, zopiclone, valproate, gabapentin, pregabalin, tiagabine, and vigabatrin) are prohibited within two weeks prior to administration of study drug;
• Antidepressant Monoamine Oxidase Inhibitors (MAOIs) are prohibited two weeks prior to the administration of the study drug.
• CYP3A4 inducers carbamazepine and modafinil are prohibited within two weeks prior to administration of the study drug and at least 24 hours after the last dose of study drug.
• Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation as either an acute or maintenance treatment of depression;
• ECT in the past 12 months;
• Use of methamphetamine, cocaine, or cannabis. Abuse of stimulant(s) within the prior 12 months;
• Any current substance use disorder (excluding nicotine and caffeine). Note: Persons will be allowed to enroll in this study if their substance use is in complete (not partial) and sustained (\> 1 year) remission;
• History of traumatic brain injury that resulted in loss of consciousness;
• Developmental delay, intellectual disability, or intellectual disorder;

Sponsors & Collaborators

• Mayo Clinic: lead

Study Sites (1)

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

Location

Related Publications (3)

• Singh B, MahmoudianDehkordi S, Voort JLV, Han X, Port JD, Frye MA, Kaddurah-Daouk R; Mood Disorders Precision Medicine Consortium (MDPMC). Metabolomic signatures of intravenous racemic ketamine associated remission in treatment-resistant depression: A pilot hypothesis generating study. Psychiatry Res. 2022 Aug;314:114655. doi: 10.1016/j.psychres.2022.114655. Epub 2022 May 28.

  PMID: 35738038 BACKGROUND

• Singh B, Port JD, Pazdernik V, Coombes BJ, Vande Voort JL, Frye MA. Racemic ketamine treatment attenuates anterior cingulate cortex GABA deficits among remitters in treatment-resistant depression: A pilot study. Psychiatry Res Neuroimaging. 2022 Mar;320:111432. doi: 10.1016/j.pscychresns.2021.111432. Epub 2021 Dec 24. No abstract available.

  PMID: 34973601 BACKGROUND

• Singh B, Port JD, Voort JLV, Coombes BJ, Geske JR, Lanza IR, Morgan RJ, Frye MA. A preliminary study of the association of increased anterior cingulate gamma-aminobutyric acid with remission of depression after ketamine administration. Psychiatry Res. 2021 Jul;301:113953. doi: 10.1016/j.psychres.2021.113953. Epub 2021 Apr 20.

  PMID: 33933839 BACKGROUND

MeSH Terms

Conditions

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

Interventions

Ketamine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Balwinder Singh, MD, MS

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Psychiatry

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: June 29, 2018
• Study Start: January 3, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: June 27, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)