Clinical trial NCT05710887: N2O for Acute Suicidality and Depression in the ED
Official title: Inhaled Nitrous Oxide for Acute Suicidality and Depression in the Emergency Department
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Suicidal Ideation
Major Depressive Disorder
Treatment Resistant Depression
Keywords: Suicidal
Depression
Nitrous
Antidepressant
MDD
TRD
Lead sponsor: University of Chicago
Sponsor class: OTHER
First posted: 2023-02-02
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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).
Primary purpose: TREATMENT

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.

Detailed description: Past studies have shown that a single dose of ketamine, an NMDA- receptor antagonist has fast and long lasting anti-depressant effect. Although a promising antidepressant and potential anti-suicidal agent, ketamine has very significant side effects including: dissociation, hallucinations, delusional thinking, cognitive impairment, and significant sympathetic nervous system activation.

Nitrous Oxide (N2O) is an NMDA-receptor antagonist with a well-known safety profile used as an analgesic. In a proof-of-concept pilot study, this study's investigator recently demonstrated that N2O also has rapid and marked antidepressant effects in patients with severe treatment-resistant depression (TRD); further sub-analyses showed N2O significantly reduced suicidal ideation (SI). While N2O administration may lead to a reduction in SI, it remains unknown whether severely suicidal patients requiring hospitalization on inpatient psychiatric units would benefit. Investigators hypothesize that N2O will rapidly and safely dampen suicidal thinking with minimal side effects in this population.

Participants will be randomized to receive either N2O or placebo. The study intervention is in tandem with prescribed treatment-as-usual (TAU) by emergency department physicians relating to diagnosis (depression, anxiety, suicidal ideation); which typically involves anxiolytic medications and/or brief psychotherapy administered by care team psychiatry providers.

Study intervention response will be assessed using a self-administered psychiatric diagnostic tool (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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Treatment Response Based on Changes in Computerized Adaptive Testing Scores
timeFrame: Up to 24-hours from baseline
Secondary outcomes:
measure: Treatment Compliance
timeFrame: Intervention completion, 45-minutes
measure: Treatment Response Correlation to Lifetime Predictors Associated with Suicide
timeFrame: Up to 24-hours from baseline
measure: Rapid Treatment Response
timeFrame: At 30-minutes to 1-hour from intervention conclusion
measure: Sustained Treatment Response
timeFrame: Up to 24-hours from intervention conclusion
Other outcomes:
measure: Adverse Events
timeFrame: Through study completion, an average of 1-week
Locations:
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
Study officials:
affiliation: University of Chicago, Department of Anesthesia and Critical Care
name: Peter Nagele, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: