Nitrous Oxide in the Treatment of Acute Suicidal Ideation

NCT ID: NCT06636357

Last Updated: 2025-01-16

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 85 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-01-13
• Study Completion Date: 2026-09-30

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: EXPERIMENTAL

50% N2O plus 50% O2

Intervention Type: DRUG

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

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.

Group Type: PLACEBO_COMPARATOR

Oxygen (O2)

Intervention Type: DRUG

50% O2 plus 50% air for 45 min

Interventions

50% N2O plus 50% O2

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

Intervention Type: DRUG

Oxygen (O2)

50% O2 plus 50% air for 45 min

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Zurich

OTHER

Sponsor Role: lead

Responsible Party

Sebastian Olbrich

Prof. Dr. med.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Psychiatric University Hospital Zurich

Zurich, , Switzerland

Site Status: RECRUITING

Countries

Switzerland

Central Contacts

Angelina Frasch

Role: CONTACT

angelina.frasch@pukzh.ch

0041583843666

Facility Contacts

Angelina Frasch

Role: primary

angelina.frasch@pukzh.ch

0041583843666

References

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.

Reference Type: DERIVED

PMID: 40669910 (View on PubMed)

Other Identifiers

2024-01005

Identifier Type: -

Identifier Source: org_study_id