Nitrous Oxide in the Treatment of Acute Suicidal Ideation (NITOS)

January 13, 2025 updated by: Sebastian Olbrich, University of Zurich
The primary aim of the NITOS study is to investigate the potential rapid antisuicidal effects of N2O in the transdiagnostic treatment of suicidal ideation. On day 1, patients will receive either nitrous oxide (50% N2O balanced with oxygen) or placebo (50% oxygen balanced with air). Seven days after the first inhalation, a second inhalation will be performed. All patients will receive N2O at least once during this trial. While the first inhalation will be double-blind, only the patients but not the raters will be blinded to the second inhalation (day 8). For mechanism of action and prediction, a nested biomarker substudy will employ multimodal techniques including analysis of hair and blood samples, and EEG.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

85

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Switzerland
      • Zürich, Switzerland, 8032
        • Recruiting
        • Psychiatric University Hospital Zurich
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • Ability to give written informed consent
  • Moderate to severe suicidal ideation defined as a score ≥3 on the Montgomery-Asberg Depression Rating Scale (MADRS; Schmidtke et al., 1985) suicide item (item #10) as well as a self-report Beck Scale for Suicide Ideation (BSS; Kliem et al., 2017) items #4 plus #5 score ≥ 2
  • Plasma homocysteine level ≤ 14 µmol/l

Exclusion criteria:

  • Organic, including symptomatic, mental disorders (F00-F09; lifetime diagnosis)
  • Schizophrenia, schizotypal and delusional disorders (F20-F29; lifetime diagnosis)
  • Mental and behavioral disorders due to psychoactive substance use. Nicotine and cannabis will be ignored (F10-F19)
  • Non-medical (i.e., recreational) use of inhalational N2O during the last 12 months
  • Past intolerance or hypersensitivity to N2O
  • Critical illness
  • Severe cardiac disease
  • Pregnancy or breastfeeding
  • Pulmonary hypertension
  • Chronic cobalamin or folate deficiency unless treated with folic acid and/or vitamin B12
  • History or evidence of any other medical or neurological condition that would expose the subject to an undue risk of a significant adverse event as determined by the clinical judgment of the investigator
  • Treatment with ketamine/esketamine during the last 4 weeks
  • Treatment with opioid medications during the last 3 months
  • Treatment with vagus nerve stimulation (VNS) or electroconvulsive therapy (ECT) within the last 3 months
  • Recent (within the last 4 weeks) or current use of benzodiazepines in excess of 5 mg lorazepam or equivalent per day
  • Finally, any other factors that, in the investigator's judgment, would unduly impact patient safety or compliance during the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 50% nitrous oxide (N2O) plus 50% oxygen
Patients will be treated with N20 (50% N2O combined with 50% oxygen) for 45 minutes. Both the study subject and the rater will be blinded to the treatment assignment.
Drug: 50% N2O plus 50% O2
Inhalation of 50% N2O plus 50% O2 for 45 min
Placebo Comparator: 50% oxygen plus 50% air
Here, patients will be treated with 50% oxygen plus air for 45 minutes. Both the study subject and the rater will be blinded to the treatment assignment.
Drug: Oxygen (O2)
50% O2 plus 50% air for 45 min

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Beck Scale for Suicidal Ideation (BSS)
Time Frame: Day 0 to Day 2
Change of BSS score between Day 0 and Day 2. Double-blind treatment with either N2O or placebo inhalation on Day 1.
Day 0 to Day 2

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Montgomery-Åsberg Depression Rating Scale (MADRS )
Time Frame: Day 0 to Day 2
Day 0 to Day 2
EEG changes associated with N2O / placebo inhalation
Time Frame: Day 1
EEG will be performed before, during, and after inhalation
Day 1
Suicide Visual Analog Scale (S-VAS)
Time Frame: Day 1
Briefly, the S-VAS uses the phrase "urge to kill myself". Next to the phrase, the patient sees a line that is anchored on the left with the word "none" and on the right with the word "extreme" . Score ranges from 0 to 100.
Day 1
Perceived Burdensomeness Visual Analog Scale (PB-VAS)
Time Frame: Day 1
The PB-VAS uses the phrase "like a burden". Next to the phrase, the patient sees a line that is anchored on the left with the word "none" and on the right with the word "extreme" . Score ranges from 0 to 100.
Day 1

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Zurich

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 13, 2025

Primary Completion (Estimated)

September 30, 2026

Study Completion (Estimated)

September 30, 2026

Study Registration Dates

First Submitted

September 6, 2024

First Submitted That Met QC Criteria

October 9, 2024

First Posted (Actual)

October 10, 2024

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 13, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2024-01005

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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