Suicidal IdeationPhase 2NCT05710887
N2O for Acute Suicidality and Depression in the ED
A Phase 2 study testing Nitrous oxide gas for inhalation in people with Suicidal Ideation and Major Depressive Disorder, run by University of Chicago at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Suicidal Ideation, Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Nitrous oxide gas for inhalation
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 27 Feb 2026to 27 Feb 2026
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients 18-65 years of age, acutely suicidal, presenting to the adult emergency department with documented history of non-psychotic major depressive disorder.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Chicago Medicine
Chicago, Illinois, 60637
About this study
Official title: Inhaled Nitrous Oxide for Acute Suicidality and Depression in the Emergency Department
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.
Read the 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.
- Being tested
- Nitrous oxide gas for inhalation, Placebo
- Keywords
- Suicidal, Depression, Nitrous, Antidepressant, MDD, TRD
- Medical subject headings
- Suicidal Ideation, Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nitrous oxide gas for inhalationDrug
Also called Nitrous Oxide, Nitrous, N2O, Laughing Gas
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.
PlaceboDrug
Also called Sham
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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment; Nitrous Oxide 50% | Active comparator | A single 45-minute session of inhaled 50% nitrous oxide. Receives: Drug: Nitrous oxide gas for inhalation |
| Control; Oxygen-air mixture | Placebo comparator | A single 45-minute session of inhaled Oxygen-air mixture Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Up to 24-hours from baseline
Secondary outcomes (4)
Treatment Compliance
Evaluate compliance of an acutely suicidal population in an Emergency Department (ED) setting, to complete a single 45-minute inhalation of nitrous oxide vs placebo.
Determined by 'ability', 'inability', or 'refusal' to complete the entire 45-minute inhalation session (nitrous oxide vs placebo).
Measured: Intervention completion, 45-minutes
Treatment Response Correlation to Lifetime Predictors Associated with Suicide
Evaluate if lifetime predictors (e.g., personal/family history of suicide attempts or suicide, history of alcohol dependence, and worst lifetime suicidal ideation) of eventual suicide correlate with the acute reduction in symptom severity following treatment.
Lifetime predictors will be determined by medical and social history, and family history related to mental health.
Symptom reduction is determined by changes in CAT-MH scores, over 24-hours from baseline.
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
Measured: Up to 24-hours from baseline
Rapid Treatment Response
Evaluate any acute reduction in symptoms.
Based on changes in CAT-MH scores (suicide, depression, anxiety) at 30-minutes to 1-hour following treatment. Study patients ability to complete self-administered CAT-MH following inhalation may impact time-point.
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
Measured: At 30-minutes to 1-hour from intervention conclusion
Sustained Treatment Response
Evaluation of sustained response based on changes in CAT-MH scores at several time-points or until the patient is transferred or discharged from the ED.
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
Measured: Up to 24-hours from intervention conclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2023
- Study start27 Feb 2026
- Primary completion27 Feb 2026
- Study completion27 Feb 2026
Why it stopped: PI has left the university
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- More trials run by University of ChicagoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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).
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Chicago
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Peter Nagele, MD, MSc, Principal investigator, University of Chicago, Department of Anesthesia and Critical Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05710887
- Sponsor's protocol ID
- IRB18-1083
- Status last verified
- Mar 2026
- First submitted
- 11 Jan 2023
- Last updated
- 4 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhaled Nitrous Oxide for Acute Suicidality and Depression in the Emergency Department
- ClinicalTrials.gov ID
- NCT05710887
- Acronym / sponsor ID
- IRB18-1083
- Keywords
- Suicidal, Depression, Nitrous, Antidepressant, MDD, TRD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: PI has left the university
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University of ChicagoUniversity, hospital or other
- Study start
- 27 Feb 2026 (actual)
- Primary completion
- 27 Feb 2026 (actual)
- Study completion
- 27 Feb 2026 (actual)
- First posted
- 2 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
- 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).
| Arm | Type | Receives |
|---|---|---|
| Treatment; Nitrous Oxide 50% | Active comparator | Drug: Nitrous oxide gas for inhalationA single 45-minute session of inhaled 50% nitrous oxide. |
| Control; Oxygen-air mixture | Placebo comparator | Drug: PlaceboA single 45-minute session of inhaled Oxygen-air mixture |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients 18-65 years of age, acutely suicidal, presenting to the adult emergency department with documented history of non-psychotic major depressive disorder.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nitrous oxide gas for inhalationAlso: Nitrous Oxide, Nitrous, N2O, Laughing GasAdministration 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. | Drug | Treatment; Nitrous Oxide 50% |
| PlaceboAlso: ShamAdministration 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. | Drug | Control; Oxygen-air mixture |
Primary outcome
Treatment Response Based on Changes in Computerized Adaptive Testing Scores
Time frame: Up to 24-hours from baseline
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
4 secondary outcomes
Treatment Compliance
Time frame: Intervention completion, 45-minutes
Treatment Response Correlation to Lifetime Predictors Associated with Suicide
Time frame: Up to 24-hours from baseline
Rapid Treatment Response
Time frame: At 30-minutes to 1-hour from intervention conclusion
Sustained Treatment Response
Time frame: Up to 24-hours from intervention conclusion
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Nagele, MD, MSc principal investigator
University of Chicago, Department of Anesthesia and Critical Care
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nitrous oxide gas for inhalation in people with Suicidal Ideation and Major Depressive Disorder, run by University of Chicago at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 4 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Response Based on Changes in Computerized Adaptive Testing Scores (time frame: Up to 24-hours from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2026.