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

University of Zurich (UZH)

Status and phase: Enrolling; Phase 2

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

Treatments: Drug: Oxygen (O2); Drug: 50% N2O plus 50% O2

Study type: Interventional

Funder types: Other

Identifiers

NCT06636357

2024-01005

Details and patient eligibility

About

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.

Enrollment: 85 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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85 participants in 2 patient groups, including a placebo group

50% nitrous oxide (N2O) plus 50% oxygen

Experimental group

Description:

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.

Treatment:

Drug: 50% N2O plus 50% O2

50% oxygen plus 50% air

Placebo Comparator group

Description:

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.

Treatment:

Drug: Oxygen (O2)