N2O for Acute Suicidality and Depression in the ED

NCT05710887 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: IRB18-1083
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators are conducting this double-blind, randomized control trial (RCT), to compare inhaled N2O+ treatment as usual (TAU) versus inhaled placebo+TAU; demonstrating the feasibility and tolerability of the intervention in an emergency department (ED) setting on an acutely suicidal population.

Conditions

Suicidal Ideation; Major Depressive Disorder; Treatment Resistant Depression

Keywords

Suicidal; Depression; Nitrous; Antidepressant; MDD; TRD

Outcome Measures

Primary Outcomes (1)

• Treatment Response Based on Changes in Computerized Adaptive Testing Scores

  Monitor changes in Computerized Adaptive Testing Mental Health (CAT-MH) scores relating to suicide, depression, and anxiety; to determine whether a single 45-minute inhalation of nitrous oxide vs placebo reduces symptoms. The CAT-MH is a validated self-reporting electronic diagnostic that adaptively selects a small optimal set of items from a large bank of approximately 1,500 items, targeted to individuals current or historical level of severity and likelihood of 'suicide', 'depression', and 'anxiety'. Generated scores include severity and liklihood percentile: * suicide = (%) low, intermediate, high * depression = (%) normal, mild, moderate, severe * anxiety = (%) normal, mild, moderate, severe

  Up to 24-hours from baseline

Secondary Outcomes (4)

• Treatment Compliance

  Intervention completion, 45-minutes

• Treatment Response Correlation to Lifetime Predictors Associated with Suicide

  Up to 24-hours from baseline

• Rapid Treatment Response

  At 30-minutes to 1-hour from intervention conclusion

• Sustained Treatment Response

  Up to 24-hours from intervention conclusion

Other Outcomes (1)

• Adverse Events

  Through study completion, an average of 1-week

Study Arms (2)

Treatment; Nitrous Oxide 50%

ACTIVE COMPARATOR

A single 45-minute session of inhaled 50% nitrous oxide.

Drug: Nitrous oxide gas for inhalation

Control; Oxygen-air mixture

PLACEBO COMPARATOR

A single 45-minute session of inhaled Oxygen-air mixture

Drug: Placebo

Interventions

Nitrous oxide gas for inhalation DRUG

Administration of inhaled 50% nitrous oxide in oxygen (FiO2 0.5) will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.

Also known as: Nitrous Oxide, Nitrous, N2O, Laughing Gas

Treatment; Nitrous Oxide 50%

Placebo DRUG

Administration of the placebo (oxygen-air mixture \[FiO2 ≈0.3\]), will be under the direct supervision of a licensed practitioner who is experienced in the use and administration of the study drug, and is familiar with the indications, effects, dosages, methods, and frequency and duration of administration, and with the hazards, contraindications, and side effects and the precautions to be taken (MD, or CRNA); with study patient monitoring of pulse oximetry, heart rate, respiratory, non-invasive blood pressure, and end-tidal carbon dioxide.

Also known as: Sham

Control; Oxygen-air mixture

Eligibility Criteria

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

You may qualify if:

• Patients 18-65 years of age, acutely suicidal, presenting to the adult emergency department with documented history of non-psychotic major depressive disorder.

You may not qualify if:

• Current psychotic or catatonic symptoms as determined by the hospital care team.
• Unable or unwilling to give consent for study participation (ability to provide consent will be established by treating physician)
• Lifetime DSM-V (medical history) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, and panic disorders.
• Meets current DSM-V substance use disorder of greater than mild severity (other than nicotine or marijuana)
• Significant pulmonary disease and/or requiring supplemental oxygen.
• Administration of other NMDA-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study.
• Contraindications for N2O (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure)
• Chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12.
• Women who are pregnant or breastfeeding
• Any other factor that in the investigators' judgment may affect patient safety or compliance.

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (1)

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

MeSH Terms

Conditions

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

Interventions

Endothelium-Dependent Relaxing Factors; Inhalation; Nitrous Oxide; salicylhydroxamic acid

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior; Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Vasodilator Agents; Cardiovascular Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses; Respiratory Mechanics; Respiration; Respiratory Physiological Phenomena; Circulatory and Respiratory Physiological Phenomena; Nitrogen Oxides; Gases; Inorganic Chemicals; Nitrogen Compounds; Oxides; Oxygen Compounds

Study Officials

• Peter Nagele, MD, MSc

  University of Chicago, Department of Anesthesia and Critical Care

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of two treatment arms (nitrous vs placebo). Dosing includes a single inhalation session of either 50% Nitrous oxide in oxygen mixture (FiO2 0.5) vs placebo (oxygen-air mixture FiO2 ≈0.3).

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: February 2, 2023
• Study Start: February 27, 2026
• Primary Completion: February 27, 2026
• Study Completion: February 27, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)