Clinical trial NCT06636357: Nitrous Oxide in the Treatment of Acute Suicidal Ideation
Official title: Nitrous Oxide in the Treatment of Acute Suicidal Ideation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Suicidality
EEG
Suicidal Ideation
Nitrous Oxide
Biomarkers / Blood
Biomarkers / Hair
Keywords: suicidality
nitrous oxide
suicidal ideation
depression
Lead sponsor: University of Zurich
Sponsor class: OTHER
First posted: 2024-10-10
Enrollment: 85
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Beck Scale for Suicidal Ideation (BSS)
timeFrame: Day 0 to Day 2
Secondary outcomes:
measure: Montgomery-Åsberg Depression Rating Scale (MADRS )
timeFrame: Day 0 to Day 2
measure: EEG changes associated with N2O / placebo inhalation
timeFrame: Day 1
measure: Suicide Visual Analog Scale (S-VAS)
timeFrame: Day 1
measure: Perceived Burdensomeness Visual Analog Scale (PB-VAS)
timeFrame: Day 1
Other outcomes:
Locations:
city: Zürich
country: Switzerland
facility: Psychiatric University Hospital Zurich
Study officials:
References: