NCT02994433

NMDA Receptor Antagonist Nitrous Oxide Targets Affective Brain Circuits

• Status: Terminated
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 49 (actual)
• Sponsor: Washington University School of Medicine · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, our group demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD. This application proposes to take the next important step in understanding how nitrous oxide exerts its effects in the human brain by using state-of-the-art brain neuroimaging (functional connectivity magnetic resonance imaging) in a group of non-depressed, healthy volunteers and comparing the results to a group of TRMD patients. This study involves exposing 20 non-depressed healthy participants and 20 TRMD participants to nitrous oxide and a placebo gas, to compare their brain images before and after each of the inhalation sessions. Sessions will be separated by at least one month to prevent treatment effects from carrying over into the following session. All willing and eligible subjects will undergo up to six functional connectivity MRI scans, and two inhalation sessions. Functional imaging in the brain will allow us to trace the interconnections between various parts of the brain, including those involved with emotion and depression. Other procedures will involve screening materials to ensure safety of the participants before beginning the study (i.e. no MRI scan contraindications) and that subjects meet eligibility criteria to being in the targeted age range, depression/non-depressed state, neurological disorder history, and no medication exclusions.

Conditions

• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant

Interventions

Type	Name	Description
DRUG	Nitrous Oxide	Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at 50% nitrous oxide/50% oxygen in this study.
DRUG	Placebo gas	Placebo gas given at 50% nitrogen \[inert\]/50% oxygen.
DEVICE	MRI	MRIs done on all participants, this is a tool we are using to measure outcomes. No treatment is from an MRI.

Timeline

• Start date: 2017-01-27
• Primary completion: 2020-02-28
• Completion: 2020-02-28
• First posted: 2016-12-15
• Last updated: 2021-08-02

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study