Inhaled Nitrous Oxide for Treatment-Resistant Depression: Optimizing Dosing Strategies

NCT ID: NCT03283670

Last Updated: 2022-04-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-11-22
• Study Completion Date: 2020-02-18

Brief Summary

The purpose of the study aims to determine whether different concentrations of nitrous oxide (N2O) have different antidepressant effects for adults with treatment-resistant major depression.

Detailed Description

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.

All patients will receive 3 randomized, one hour nitrous oxide inhalations to placebo (0% N2O), low dose (25% N2O), and high dose (50% N2O). Inhalation sessions will be at least 4 weeks apart. Mood will be assessed at baseline, 2 and 24 hours, and 1, 2, and 4 weeks post-inhalation for each dose.

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1. 25% nitrous oxide, 25% nitrogen, 25% oxygen

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Group Type: EXPERIMENTAL

Nitrous Oxide 25%

Intervention Type: DRUG

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 a concentration of 25% nitrous oxide/50% oxygen/25% nitrogen.

2. 50% nitrous oxide, 50% oxygen

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Group Type: EXPERIMENTAL

Nitrous Oxide 50%

Intervention Type: DRUG

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 a concentration of 50% nitrous oxide/50% oxygen.

3. Placebo gas: 50% nitrogen(inert), 50% oxygen

Participants will be studied for 14 visits over approximately 18 weeks. The participants will receive 1 hour-long gas inhalation mixtures at 3 different times, which are randomly assigned.

Group Type: PLACEBO_COMPARATOR

Placebo Gas

Intervention Type: DRUG

Placebo gas given at 50% nitrogen \[inert\]/50% oxygen.

Interventions

Nitrous Oxide 25%

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 a concentration of 25% nitrous oxide/50% oxygen/25% nitrogen.

Intervention Type: DRUG

Nitrous Oxide 50%

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 a concentration of 50% nitrous oxide/50% oxygen.

Intervention Type: DRUG

Placebo Gas

Placebo gas given at 50% nitrogen \[inert\]/50% oxygen.

Intervention Type: DRUG

Other Intervention Names

One hour inhalation of 25% nitrous oxide; One hour inhalation of 50% nitrous oxide; One hour inhalation of placebo gas

Eligibility Criteria

Inclusion Criteria

1. Adults 18-75 years of age;

2. Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;

3. A score of >= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);

4. Documented (i.e., chart review) lifetime failure to respond to >=3 adequate dose/duration antidepressant treatment trials, ≥1 medication failure in the current depressive episode;

5. Good command of the English language.

Exclusion Criteria

1. Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;

2. Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;

3. Ability to become pregnant and not using effective contraception;

4. Contraindication against the use of nitrous oxide:

1. Pneumothorax

2. Bowel obstruction

3. Middle ear occlusion

4. Elevated intracranial pressure

5. Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12

6. Pregnant patients

7. Breastfeeding women

5. Inability to provide informed consent;

6. Any other factor that in the investigators' judgment may affect patient safety or compliance

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brain & Behavior Research Foundation

OTHER

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Ben Palanca

Associate Professor of Anesthesiology and Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ben Palanca, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

References

de Leon VC, Kumar A, Nagele P, Palanca BJ, Gott B, Janski A, Zorumski CF, Conway CR. Nitrous Oxide Reduced Suicidal Ideation in Treatment-Resistant Major Depression in Exploratory Analysis. J Clin Psychiatry. 2023 Aug 16;84(5):22br14725. doi: 10.4088/JCP.22br14725. No abstract available.

Reference Type: DERIVED

PMID: 37585253 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

201608024

Identifier Type: -

Identifier Source: org_study_id