Nitrous Oxide in the Treatment of Acute Suicidal Ideation

NCT06636357 | Recruiting Phase 2

• 1 other identifier: 2024-01005
• Study Type: interventional
• Target: 85
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Suicidality; EEG; Suicidal Ideation; Nitrous Oxide; Biomarkers / Blood; Biomarkers / Hair

Keywords

suicidality; nitrous oxide; suicidal ideation; depression

Outcome Measures

Primary Outcomes (1)

• Beck Scale for Suicidal Ideation (BSS)

  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 Outcomes (4)

• Montgomery-Åsberg Depression Rating Scale (MADRS )

  Day 0 to Day 2

• EEG changes associated with N2O / placebo inhalation

  Day 1

• Suicide Visual Analog Scale (S-VAS)

  Day 1

• Perceived Burdensomeness Visual Analog Scale (PB-VAS)

  Day 1

Study Arms (2)

50% nitrous oxide (N2O) plus 50% oxygen

EXPERIMENTAL

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

50% oxygen plus 50% air

PLACEBO COMPARATOR

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)

Interventions

50% N2O plus 50% O2 DRUG

Inhalation of 50% N2O plus 50% O2 for 45 min

50% nitrous oxide (N2O) plus 50% oxygen

Oxygen (O2) DRUG

50% O2 plus 50% air for 45 min

50% oxygen plus 50% air

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Zurich: lead

Study Sites (1)

Psychiatric University Hospital Zurich

Zurich, 8032, Switzerland

RECRUITING

Related Publications (1)

• Kronenberg G, Bankwitz A, Provaznikova B, Muller M, Quednow BB, Seifritz E, Olbrich S. Inhalational nitrous oxide as a transdiagnostic approach for the treatment of suicidal ideation and suicidality in psychiatric inpatients: protocol for a double-blind randomised, controlled clinical single-centre trial. BMJ Open. 2025 Jul 16;15(7):e096825. doi: 10.1136/bmjopen-2024-096825.

  PMID: 40669910 DERIVED

MeSH Terms

Conditions

Suicidal Ideation; Depression

Interventions

Oxygen

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Chalcogens; Elements; Inorganic Chemicals; Gases

Central Study Contacts

Angelina Frasch

CONTACT

0041583843666; angelina.frasch@pukzh.ch

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: September 6, 2024
• First Posted: October 10, 2024
• Study Start: January 13, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 16, 2025

Record last verified: 2024-10

Locations

CH (1)