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

NCT03283670 | Completed Phase 2 Results

• 1 other identifier: 201608024
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Keywords

Depression; treatment-resistant

Outcome Measures

Primary Outcomes (1)

• Change in Depression Symptoms Measured by the Hamilton Depression Rating Scale- 21 Items

  Change in depression symptoms measured by the Hamilton Depression Rating Scale- 21 items. The HAMD-21 is designed to rate the severity of depression in patients. Although it contains 21 areas, calculate the patient's score as the total score on the first 17 answers. Scale: 0=absent, 4=worst level possible) the scores on the individual items are summed. Changes will be based on measurements obtained at baseline, approximately 2 hours after inhalation, and approximately 24 hours after inhalation. Changes are based on subtracti on of baseline score.

  2 and 24 hours after inhalation

Study Arms (3)

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

EXPERIMENTAL

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.

Drug: Nitrous Oxide 25%

2. 50% nitrous oxide, 50% oxygen

EXPERIMENTAL

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.

Drug: Nitrous Oxide 50%

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

PLACEBO COMPARATOR

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.

Drug: Placebo Gas

Interventions

Nitrous Oxide 25% 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.

Also known as: One hour inhalation of 25% nitrous oxide

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

Nitrous Oxide 50% 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.

Also known as: One hour inhalation of 50% nitrous oxide

2. 50% nitrous oxide, 50% oxygen

Placebo Gas DRUG

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

Also known as: One hour inhalation of placebo gas

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

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults 18-75 years of age;
• Current diagnosis of unipolar major depressive disorder (MDD) without psychosis as confirmed by structured clinical interview for DSM-IV disorders;
• A score of \>= 9 on the Montgomery-Åsberg Depression Rating Scale (MADRS);
• 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;
• Good command of the English language.

You may not qualify if:

• Meets criteria for any DSM-IV diagnosis for schizophrenia, bipolar, schizoaffective, obsessive-compulsive, personality, or panic disorders;
• Any recent (within past 12 months) history of substance dependence or abuse (except tobacco), determined by reported history or urine drug screen;
• Ability to become pregnant and not using effective contraception;
• Contraindication against the use of nitrous oxide:
• Pneumothorax
• Bowel obstruction
• Middle ear occlusion
• Elevated intracranial pressure
• Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12
• Pregnant patients
• Breastfeeding women
• Inability to provide informed consent;
• Any other factor that in the investigators' judgment may affect patient safety or compliance

Sponsors & Collaborators

• Washington University School of Medicine: lead
• Brain & Behavior Research Foundation: collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• 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.

  PMID: 37585253 DERIVED

MeSH Terms

Conditions

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

Interventions

Nitrous Oxide

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Results Point of Contact

• Title: Ben Palanca, MD PhD
• Organization: Washington University

palancab@wustl.edu

314 273-9076

Study Officials

• Ben Palanca, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Anesthesiology and Psychiatry

Model Details: Each participant receives the 3 inhalation types in randomized, one hour sessions separated by at least 4 weeks

Study Record Dates

• First Submitted: November 9, 2016
• First Posted: September 14, 2017
• Study Start: November 22, 2016
• Primary Completion: February 18, 2020
• Study Completion: February 18, 2020
• Last Updated: April 4, 2022
• Results First Posted: April 4, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)