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Nitrous Oxide- Suicidal Ideation

Primary Purpose

Major Depressive Disorder, Depression, Mood Disorders

Status
Enrolling by invitation
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Nitrous Oxide
Placebo gas
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Major Depressive Disorder focused on measuring Nitrous Oxide, Anesthetics

Eligibility Criteria

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

Inclusion Criteria:

  1. Patients aged 18-65 years old;
  2. current diagnosis of unipolar, major depressive disorder (MDD) without psychosis as defined by the Mini-International Neuropsychiatric Interview (MINI) and The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) DSM-IV determined by clinical interview and by a baseline score of ≥18 on the HDRS-21 (Hamilton Depression Rating Scale 21-item;
  3. moderate to severe SI defined as a score ≥3 on the HDRS-21 suicide item (item #3);
  4. will have good command of the English language;
  5. will have been voluntarily admitted to the inpatient Psychiatric Units at Barnes-Jewish Hospital/Washington University in St. Louis, MO.

Exclusion Criteria:

  1. Lifetime DSM-IV (obtained via MINI) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, evidence of severe personality disorder (e.g., history of recurrent self-mutilation/cutting, significant and recurrent tumultuous relationships), and panic disorders;
  2. past 12-month substance abuse/dependence other than nicotine;
  3. active psychotic symptoms;
  4. significant pulmonary disease and/or requiring supplemental oxygen;
  5. administration of other N-Methyl-D-aspartate (NMDA)-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study;
  6. currently receiving electroconvulsive therapy;
  7. contraindications for nitrous oxide (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure, chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12);
  8. past 12-month history of head trauma;
  9. women who are pregnant or breastfeeding;
  10. any other factor that in the investigators' judgment may affect patient safety or compliance.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nitrous Oxide

Placebo Gas

Arm Description

Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at 50% nitrous oxide/50% oxygen in this study. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive inhaled nitrous oxide.

Placebo gas given at 50% nitrogen [inert]/50% oxygen. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive placebo gas.

Outcomes

Primary Outcome Measures

Severity and number of adverse events in both nitrous oxide and placebo groups
Safety and tolerability of inhaled nitrous oxide will be measured by collecting adverse events in both groups at each study visit throughout the study.
Differential change in suicidal ideation
Participants receiving inpatient treatment as usual plus nitrous oxide compared to participants receiving inpatient treatment as usual plus placebo as measured by scores on the 19-item Scale for Suicidal Ideation (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation).
Identification of pre-treatment key clinical correlates of anti-suicidal response to nitrous oxide
Correlations of change in Scale for Suicidal Ideation score (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation) at end of inpatient period with: 1) presence of family history of alcohol dependence; 2) a personal/family history of suicide attempt or a family history of suicide.

Secondary Outcome Measures

Full Information

First Posted
November 6, 2018
Last Updated
July 27, 2022
Sponsor
Washington University School of Medicine
Collaborators
American Foundation for Suicide Prevention
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1. Study Identification

Unique Protocol Identification Number
NCT03736538
Brief Title
Nitrous Oxide- Suicidal Ideation
Official Title
Adjunctive Nitrous Oxide for Acute Suicidal Ideation in Unipolar Depressed Hospitalized Patients
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Enrolling by invitation
Study Start Date
October 30, 2018 (Actual)
Primary Completion Date
June 2024 (Anticipated)
Study Completion Date
July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
American Foundation for Suicide Prevention

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Most clinical major depression responds to standard treatments (medication and psychotherapy); however, a significant subset of depressed patients (15-20%) do not respond to these treatments and are referred to as treatment-resistant major depression (TRMD). New treatments for TRMD are needed, and one promising line of research are drugs known as N-methyl-D-aspartate (NMDA) glutamate receptor antagonists. In a recent pilot study, the investigators of this study demonstrated that the NMDA antagonist nitrous oxide is effective in TRMD, reducing depressive symptoms, guilt, and suicidal thinking. To more closely investigate suicidal thinking, this study is designed as a double-blind, randomized, prospective, inpatient trial comparing inhaled nitrous oxide (N2O) plus treatment as usual versus inhaled placebo plus treatment as usual. All unipolar depressed, acutely suicidal inpatients will receive standard treatment for their depression/ suicidal thinking (TAU). Additionally, participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive either inhaled nitrous oxide (50% nitrous oxide/50% oxygen = active treatment) or placebo gas (50% nitrogen/50% oxygen). A target total of 50 patients with suicidal ideation and unipolar depression will be enrolled, 25 of whom will be assigned to the TAU control group and 25 of whom will be assigned to the N2O + TAU experimental group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Depression, Mood Disorders, Suicidal Ideation
Keywords
Nitrous Oxide, Anesthetics

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nitrous Oxide
Arm Type
Experimental
Arm Description
Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at 50% nitrous oxide/50% oxygen in this study. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive inhaled nitrous oxide.
Arm Title
Placebo Gas
Arm Type
Placebo Comparator
Arm Description
Placebo gas given at 50% nitrogen [inert]/50% oxygen. Participants will undergo a maximum of four one hour inhalation sessions as inpatients and 2 booster sessions as outpatients during which they will receive placebo gas.
Intervention Type
Drug
Intervention Name(s)
Nitrous Oxide
Other Intervention Name(s)
Laughing Gas
Intervention Description
Nitrous oxide, an odorless, colorless gas typically used as an induction agent for general anesthesia or for dental sedation, is a known N-methyl-D-aspartate (NMDA) antagonist. It will be given at 50% nitrous oxide/50% oxygen in this study.
Intervention Type
Drug
Intervention Name(s)
Placebo gas
Intervention Description
Placebo gas given at 50% nitrogen [inert]/50% oxygen.
Primary Outcome Measure Information:
Title
Severity and number of adverse events in both nitrous oxide and placebo groups
Description
Safety and tolerability of inhaled nitrous oxide will be measured by collecting adverse events in both groups at each study visit throughout the study.
Time Frame
Throughout study duration (approximately 60 days)
Title
Differential change in suicidal ideation
Description
Participants receiving inpatient treatment as usual plus nitrous oxide compared to participants receiving inpatient treatment as usual plus placebo as measured by scores on the 19-item Scale for Suicidal Ideation (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation).
Time Frame
Baseline to Day 7, approximately 7 days (following the inpatient period inhalation sessions)
Title
Identification of pre-treatment key clinical correlates of anti-suicidal response to nitrous oxide
Description
Correlations of change in Scale for Suicidal Ideation score (SSI; total score range is 0 to 38, higher scores indicate greater suicidal ideation) at end of inpatient period with: 1) presence of family history of alcohol dependence; 2) a personal/family history of suicide attempt or a family history of suicide.
Time Frame
Change of scores on the SSI for the approximate 7 days of inpatient period

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 aged 18-65 years old; current diagnosis of unipolar, major depressive disorder (MDD) without psychosis as defined by the Mini-International Neuropsychiatric Interview (MINI) and The Fourth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) DSM-IV determined by clinical interview and by a baseline score of ≥18 on the HDRS-21 (Hamilton Depression Rating Scale 21-item; moderate to severe SI defined as a score ≥3 on the HDRS-21 suicide item (item #3); will have good command of the English language; will have been voluntarily admitted to the inpatient Psychiatric Units at Barnes-Jewish Hospital/Washington University in St. Louis, MO. Exclusion Criteria: Lifetime DSM-IV (obtained via MINI) diagnoses of schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, evidence of severe personality disorder (e.g., history of recurrent self-mutilation/cutting, significant and recurrent tumultuous relationships), and panic disorders; past 12-month substance abuse/dependence other than nicotine; active psychotic symptoms; significant pulmonary disease and/or requiring supplemental oxygen; administration of other N-Methyl-D-aspartate (NMDA)-receptor antagonist treatment (e.g., ketamine) within two weeks of entry into study; currently receiving electroconvulsive therapy; contraindications for nitrous oxide (pneumothorax, bowel obstruction, middle ear occlusion, elevated intracranial pressure, chronic cobalamin and/or folate deficiency treated with folic acid or vitamin B12); past 12-month history of head trauma; women who are pregnant or breastfeeding; any other factor that in the investigators' judgment may affect patient safety or compliance.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles R Conway, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

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Nitrous Oxide- Suicidal Ideation

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