Not provided
Not provided
Not provided
Not provided
Not provided
PI has left the university
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment; Nitrous Oxide 50% | Active Comparator | A single 45-minute session of inhaled 50% nitrous oxide. |
|
| Control; Oxygen-air mixture | Placebo Comparator | A single 45-minute session of inhaled Oxygen-air mixture |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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:
| Up to 24-hours from baseline |
| Measure | Description | Time Frame |
|---|---|---|
| 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). | Intervention completion, 45-minutes |
| Measure | Description | Time Frame |
|---|---|---|
| Adverse Events | Monitor adverse events and severity associated with study participation, including nausea and vomiting; or other symptoms determined 'probably', 'possibly', 'unrelated', or 'related' to the study intervention. This includes any unplanned escalation of care including pharmacological therapy for nausea, vomiting. Study patient safety is monitored by the investigators (MD) with experience in critical care anesthesia, as well as an experienced clinical research team responsible for data collection and reporting of events. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Peter Nagele, MD, MSc | University of Chicago, Department of Anesthesia and Critical Care | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Chicago Medicine | Chicago | Illinois | 60637 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D059020 | Suicidal Ideation |
| D003865 | Depressive Disorder, Major |
| D061218 | Depressive Disorder, Treatment-Resistant |
| D003863 | Depression |
| ID | Term |
|---|---|
| D013405 | Suicide |
| D016728 | Self-Injurious Behavior |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
Not provided
Not provided
| ID | Term |
|---|---|
| D045462 | Endothelium-Dependent Relaxing Factors |
| D001239 | Inhalation |
| D009609 | Nitrous Oxide |
| C005703 | salicylhydroxamic acid |
| ID | Term |
|---|---|
| D014665 | Vasodilator Agents |
| D002317 | Cardiovascular Agents |
| D045506 | Therapeutic Uses |
| D020228 | Pharmacologic Actions |
Not provided
Not provided
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).
Not provided
Not provided
Not provided
|
|
| 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. |
|
|
| 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:
| 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:
| 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:
| Up to 24-hours from intervention conclusion |
| Through study completion, an average of 1-week |
| D003866 |
| Depressive Disorder |
| D019964 | Mood Disorders |
| D001523 | Mental Disorders |
| D020164 |
| Chemical Actions and Uses |
| D015656 | Respiratory Mechanics |
| D012119 | Respiration |
| D012143 | Respiratory Physiological Phenomena |
| D002943 | Circulatory and Respiratory Physiological Phenomena |
| D009589 | Nitrogen Oxides |
| D005740 | Gases |
| D007287 | Inorganic Chemicals |
| D017672 | Nitrogen Compounds |
| D010087 | Oxides |
| D017601 | Oxygen Compounds |