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N2O for Acute Suicidality and Depression in the ED

Primary Purpose

Suicidal Ideation, Major Depressive Disorder, Treatment Resistant Depression

Status
Not yet recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Nitrous oxide gas for inhalation
Placebo
Sponsored by
University of Chicago
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Suicidal Ideation focused on measuring Suicidal, Depression, Nitrous, Antidepressant, MDD, TRD

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • University of Chicago Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Treatment; Nitrous Oxide 50%

Control; Oxygen-air mixture

Arm Description

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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).
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
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
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

Full Information

First Posted
January 11, 2023
Last Updated
June 1, 2023
Sponsor
University of Chicago
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1. Study Identification

Unique Protocol Identification Number
NCT05710887
Brief Title
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

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
July 1, 2023 (Anticipated)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
July 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Chicago

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suicidal Ideation, Major Depressive Disorder, Treatment Resistant Depression
Keywords
Suicidal, Depression, Nitrous, Antidepressant, MDD, TRD

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Treatment; Nitrous Oxide 50%
Arm Type
Active Comparator
Arm Description
A single 45-minute session of inhaled 50% nitrous oxide.
Arm Title
Control; Oxygen-air mixture
Arm Type
Placebo Comparator
Arm Description
A single 45-minute session of inhaled Oxygen-air mixture
Intervention Type
Drug
Intervention Name(s)
Nitrous oxide gas for inhalation
Other Intervention Name(s)
Nitrous Oxide, Nitrous, N2O, Laughing Gas
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sham
Intervention Description
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.
Primary Outcome Measure Information:
Title
Treatment Response Based on Changes in Computerized Adaptive Testing Scores
Description
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
Time Frame
Up to 24-hours from baseline
Secondary Outcome Measure Information:
Title
Treatment Compliance
Description
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).
Time Frame
Intervention completion, 45-minutes
Title
Treatment Response Correlation to Lifetime Predictors Associated with Suicide
Description
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
Time Frame
Up to 24-hours from baseline
Title
Rapid Treatment Response
Description
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
Time Frame
At 30-minutes to 1-hour from intervention conclusion
Title
Sustained Treatment Response
Description
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
Time Frame
Up to 24-hours from intervention conclusion
Other Pre-specified Outcome Measures:
Title
Adverse Events
Description
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.
Time Frame
Through study completion, an average of 1-week

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Frank Brown
Phone
773-834-5778
Email
ftbrownjr@uchicagomedicine.org
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Nagele
Phone
773-702-2545
Email
pnagele@bsd.uchicago.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Peter Nagele, MD, MSc
Organizational Affiliation
University of Chicago, Department of Anesthesia and Critical Care
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Frank Brown
Phone
773-834-5778
Email
ftbrownjr@uchicagomedicine.org
First Name & Middle Initial & Last Name & Degree
Peter Nagele, MD, MSc
First Name & Middle Initial & Last Name & Degree
David Beiser, MD, MSc, FACEP
First Name & Middle Initial & Last Name & Degree
Royce Lee, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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N2O for Acute Suicidality and Depression in the ED

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