Actively Recruiting

Phase 2
Age: 18Years - 65Years
All Genders
ID06668571

Central and Peripheral GABA and Glutamate Modulation With Intravenous Ketamine for Treatment-Resistant Depression (G2K): A Randomized, Double-Blind, Placebo-Controlled Study

Led by Mayo Clinic · Updated on 2025-10-14

30

Participants Needed

1

Research Sites

N/A

Total Duration

On this page

Sponsors

M

Mayo Clinic

Lead Sponsor

N

National Center for Advancing Translational Sciences (NCATS)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are studying adults with treatment-resistant major depressive disorder to understand how changes in brain and blood levels of certain brain chemicals called GABA and glutamate relate to improvements in depression symptoms after receiving intravenous ketamine or a placebo. The study uses advanced imaging and blood tests to measure these chemicals and tracks depression changes using a recognized depression rating scale. The research also explores markers that might be linked to ketamine treatment response. Participants will be randomly assigned to receive either a single intravenous infusion of racemic ketamine or a normal saline placebo over 40 minutes while undergoing MRI scanning. After this, all participants can choose to receive an open-label ketamine infusion 1 to 7 days later. The ketamine dose is calculated based on weight, with a maximum dose limit. This randomized, double-blind, placebo-controlled design aims to compare the effects of ketamine versus placebo on brain chemistry and depression. During the study, participants will undergo assessments including brain imaging, blood tests, and depression rating scales before, during, and up to 24 hours after infusion. Researchers will measure changes in brain and blood levels of GABA and glutamate, depression severity, and other related markers. Safety and side effects will be monitored throughout. Participants’ involvement includes clinical evaluations and optional follow-up treatments, with the study lasting from initial screening through post-infusion assessments.

CONDITIONS

Brief Title

Intravenous Ketamine for Treatment-Resistant Depression

Who Can Participate

Age: 18Years - 65Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Ability to provide informed consent
  • Diagnosed with major depressive disorder without psychotic features according to SCID DSM-IV-TR
  • PHQ-9 total score of 15 or higher at screening
  • Treatment-resistant depression defined by failure of at least two prior antidepressant treatments during current episode, including adequate pharmacotherapy, TMS, or ECT
  • Able to pass a comprehension test about ketamine effects and study objectives
Not Eligible

You will not qualify if you...

  • Inability to speak English
  • Unable to provide consent or lack of legal guardian
  • Body mass index over 40 kg/m2
  • Primary diagnosis of personality disorder
  • Diagnosis of schizophrenia, schizoaffective disorder, bipolar disorder, or active psychotic symptoms
  • Active post-traumatic stress disorder symptoms
  • Taking more than 2 mg lorazepam equivalents daily or any morning benzodiazepine dosing
  • Use of medications affecting glutamate or GABA within two weeks prior and 24 hours after study drug
  • Use of MAO inhibitors within two weeks prior
  • Use of opioid antagonists within two weeks prior and 24 hours after study drug
  • Use of CYP3A4 inducers carbamazepine or modafinil within two weeks prior and 24 hours after study drug
  • Currently undergoing TMS, vagal nerve stimulation, or deep brain stimulation
  • Electroconvulsive therapy in past 6 months
  • Unstable or active medical conditions posing high medical risk
  • History of brain bleeding, arteriovenous malformation, or aneurysm
  • Use or abuse of methamphetamine, cocaine, cannabis, or stimulants within past year
  • Current substance use disorder except nicotine and caffeine unless in full remission over 1 year
  • History of traumatic brain injury with loss of consciousness and brain bleeding
  • History of tonic-clonic seizures
  • Developmental delay, intellectual disability, or disorder
  • Diagnosis of delirium, encephalopathy, or related condition in past 12 months
  • Minor or major neurocognitive disorder
  • Ketamine treatment for depression within past 2 months
  • History of poor response or intolerance to ketamine
  • Untreated hypothyroidism
  • Liver problems including hepatic insufficiency or cirrhosis
  • Poorly managed gastroesophageal reflux disease
  • Complex Regional Pain Syndrome diagnosis
  • Pregnancy or nursing
  • Claustrophobia interfering with MRI
  • Contraindications to MRI safety
  • Poorly controlled hypertension

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

1
2
3
+1

Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Treatment

Duration - 1 week

Participants receive a single 40-minute intravenous infusion of either ketamine or placebo in an MRI scanner, followed by an optional open-label ketamine infusion 1 to 7 days later.

1 infusion visit and 1 optional follow-up infusion visit

Follow-up

Duration - 24 hours post-infusion

Participants are monitored for changes in depression symptoms and biochemical markers up to 24 hours after the infusion(s).

1 follow-up visit within 24 hours post-infusion

Trial Site Locations

Total: 1 location

1

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Actively Recruiting

Loading map...

Research Team

N

Nicole Reinicke

How is the study designed?

Study Type

INTERVENTIONAL

Masking

TRIPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

2

Similar Trials

An Interventional Open-label Multicenter Study to Evaluate t...

Depressive Disorder, Treatment-Resistant

Actively Recruiting

6 locations

Investigation of Neurobiological Biomarker Changes After Acc...

Major Depressive Disorder (MDD)

Actively Recruiting

1 location

Accelerated versus Conventional Theta Burst Stimulation for ...

Late Life Depression (LLD)

Actively Recruiting

2 locations

Frequently Asked Questions

Have more questions? Get in touch with our team for quick support

Not the Right Trial for You?

Explore thousands of other clinical trials that might be a better match.
Sign up to get personalized trial recommendations delivered to your inbox.

Already have an account? Log in here

Published Research Related To This Trial

Treatment-resistant depression patients with baseline suicidal ideation required more treatments to achieve therapeutic response with ketamine/esketamine.

Balwinder Singh, Jennifer L Vande Voort, Vanessa K Pazdernik...

https://pubmed.ncbi.nlm.nih.gov/38302067

The Association Between Body Mass Index and Remission Rates in Patients With Treatment-Resistant Depression Who Received Intravenous Ketamine.

Balwinder Singh, William V Bobo, Keith G Rasmussen...

https://pubmed.ncbi.nlm.nih.gov/31721482

Concomitant benzodiazepine use attenuates ketamine response: implications for large scale study design and clinical development.

Mark A Frye, Pierre Blier, Susannah J Tye

https://pubmed.ncbi.nlm.nih.gov/25928701

Change in neurocognitive functioning in patients with treatment-resistant depression with serial intravenous ketamine infusions: The Bio-K multicenter trial.

Balwinder Singh, Sagar V Parikh, Jennifer L Vande Voort...

https://pubmed.ncbi.nlm.nih.gov/38479192

Clinical outcomes in the biomarkers of ketamine (Bio-K) study of open-label IV ketamine for refractory depression.

Sagar V Parikh, Jennifer L Vande Voort, Anastasia K Yocum...

https://pubmed.ncbi.nlm.nih.gov/38142892

Comparative Effectiveness of Intravenous Ketamine and Intranasal Esketamine in Clinical Practice Among Patients With Treatment-Refractory Depression: An Observational Study.

Balwinder Singh, Simon Kung, Vanessa Pazdernik...

https://pubmed.ncbi.nlm.nih.gov/36724113

Elevated prefrontal cortex GABA in patients with major depressive disorder after TMS treatment measured with proton magnetic resonance spectroscopy.

Marc J Dubin, Xiangling Mao, Samprit Banerjee...

https://pubmed.ncbi.nlm.nih.gov/26900793