Nitrous Oxide as Treatment for Major Depression - a Pilot Study

NCT02139540 | Completed Phase 2 Results DMC

• 1 other identifier: 201204023
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief Summary

Major depressive disorder (MDD) is a global medical problem with significant shortcomings in current therapy. Chief among these is the delay between initiation of pharmacologic therapy and clinical improvement in symptoms. Recently ketamine, an NDMA-receptor antagonist has been shown to rapidly and effectively reverse the symptoms of MDD. Nitrous oxide, another NMDA-receptor antagonist, may produce the same effect with a cleaner side-effect profile and perhaps without the need for intravenous access and anesthesia personnel. Therefore, we propose conducting a pilot randomized placebo controlled double-blind crossover study in which patients will receive up to 50% nitrous oxide in oxygen or up to 50% oxygen in air for a period of one hour in addition to standard medical therapy. Depression severity will be assessed by a blinded observer pre-treatment, 30 minutes and 2 hours post treatment using the Hamilton depression rating scale.

Conditions

Depression; Major Depressive Disorder

Keywords

Treatment

Outcome Measures

Primary Outcomes (1)

• Change in Hamilton Depression Rating Scale HDRS-21

  (21-point Hamilton Depression Rating Scale) Scoring is based on the first 17 items on the 21 point scale. Eight items are scored on a 5-point scale, ranging form 0=not present to 4= severe. Nine are scored from 0-2.

  baseline and 24 hours

Secondary Outcomes (1)

• Change in Quick Inventory of Depressive Symptomatology - Self Report - QIDS -SR

  baseline and 24 hours

Study Arms (2)

N2O/Placebo

OTHER

First session: Nitrous oxide Second session: placebo

Drug: Nitrous Oxide; Drug: Placebo

Placebo/N2O

OTHER

First session: Placebo Second session: Nitrous Oxide

Drug: Nitrous Oxide; Drug: Placebo

Interventions

Nitrous Oxide DRUG

Patients will receive either up to 50% nitrous oxide/50% oxygen for 1 hour or "placebo" (50% nitrogen \[inert\]/50% oxygen) in two separate sessions. Both sessions will be 1 week apart.

Also known as: Laughing Gas

N2O/Placebo; Placebo/N2O

Placebo DRUG

50% nitrogen \[inert\]/50% oxygen - otherwise completely identical administration and setup

Also known as: 50% nitrogen [inert]/50% oxygen

N2O/Placebo; Placebo/N2O

Eligibility Criteria

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

You may qualify if:

• Adults 18-65 years of age
• Major depressive disorder without psychosis with as determined by structured interview using the Mini-International Neuropsychiatric Interview (MINI).
• (baseline )
• HDRS-21 score of \>18
• Good command of the English language

You may not qualify if:

• History of:
• Bipolar disorder
• Schizoprenia
• Schizoaffective disorder
• Obsessive-compulsive disorder, panic disorder
• Substance abuse or dependence (except for remote substance abuse or dependence with remission at least 1 year prior to the study and except for nicotine use disorders)
• Axis II diagnoses that may interfere with the patient's ability to improve on nitrous oxide
• Acute medical illness that may pose subject at risk during nitrous oxide administration
• Active suicidal intention (inability to contract for safety)
• Active psychotic symptoms
• Patients with significant pulmonary disease and/or requiring supplemental oxygen
• Contraindication against the use of nitrous oxide:
• Pneumothorax
• Bowel obstruction
• Middle ear occlusion

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Barnes-Jewish Hospital

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

Depression; Depressive Disorder, Major

Interventions

Nitrous Oxide; Nitrogen

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Principal Investigator
• Organization: Washington University

7737022544

Study Officials

• Peter Nagele, MD, MSc

  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: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2014
• First Posted: May 15, 2014
• Study Start: November 1, 2012
• Primary Completion: April 1, 2015
• Study Completion: April 1, 2015
• Last Updated: January 27, 2020
• Results First Posted: January 27, 2020

Record last verified: 2020-01

Locations

US (1)