NCT04378426: N2OP

Nitrous Oxide for PTSD

Terminated Phase 2 Results posted Last updated 3 March 2023

What this trial tests

Phase 2 trial testing Nitrous Oxide in PTSD in 1 participant. Terminated before completion.

Timeline

7 October 2021

Primary endpoint
31 August 2022

31 August 2022

Quick facts

Lead sponsor	VA Office of Research and Development
Phase	Phase 2
Status	Terminated
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	1
Start date	7 October 2021
Primary completion	31 August 2022
Estimated completion	31 August 2022
Sites	1 location across United States

Drugs / interventions tested

• Nitrous Oxide (NITROUS OXIDE) — full drug profile →
• Midazolam (midazolam) — full drug profile →
• Nitrogen — full drug profile →
• Oxygen — full drug profile →
• Saline

Conditions studied

• PTSD — all drugs for PTSD →

Sponsor

VA Office of Research and Development — full company profile →

Who can join

Adults 18 to 65, any sex, with PTSD. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Improvement in the Severity of PTSD as Measured by the Clinician Administered PTSD Scale DSM5 (CAPS-5) Primary · 1 week

Improvement in PTSD severity is measured by the Clinician Administered PTSD Scale DSM-5 (CAPS-5). It measures frequency and intensity of PTSD-related symptoms. For the CAPS-5 the minimum units are 0 and maximum units are 80. The higher the number on the CAPS-5, the more severe the PTSD symptoms. Response is defined as a change in the CAPS-5 of at least 12 points, which represents meaningful improvement in clinical PTSD symptoms.

Group	Value	95% CI
Nitrous Oxide	46	± 0

Adverse events — posted to ClinicalTrials.gov

Time frame: 1 week. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Nitrous Oxide

Serious: 0/1 (0%)

Deaths: 0/1

Midazolam

Serious: 0

Deaths: 0

Other adverse events (7 terms — click to expand)

Reaction	System	Nitrous Oxide	Midazolam
nausea	Gastrointestinal disorders	—	—
dizziness	Nervous system disorders	—	—
poor coordination	Nervous system disorders	—	—
poor concentration	Nervous system disorders	—	—
fatigue	Nervous system disorders	—	—
general malaise	Nervous system disorders	—	—
tingling in toes	Nervous system disorders	—	—

Data from ClinicalTrials.gov NCT04378426 adverse events section.

Sponsor's own description

Post-traumatic stress disorder (PTSD) seriously disrupts the lives of many Veterans. Current first-line treatments, serotonin reuptake inhibitors or prolonged exposure therapy, take weeks to months to bring meaningful improvement, leaving Veterans experiencing prolonged suffering. A promising new treatment approach for rapidly reducing PTSD symptoms is nitrous oxide, an inhalation anesthetic and putative glutamate modulator that diminishes depression symptoms within 1 day and has limited side effects. If shown to be similarly effective in PTSD, nitrous oxide may add dramatically to the treatment armamentarium by bringing rapid symptom decrease before longer-term therapies take hold. The proposed projects test the efficacy of nitrous oxide in relieving Veteran's PTSD symptoms and, in parallel, explore how nitrous oxide may modify cognitive and pain outcomes.

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Alleviating anxiety and taming trauma: Novel pharmacotherapeutics for anxiety disorders and posttraumatic stress disorder.
   Singewald N, Sartori SB, Reif A, Holmes A. · · 2023 · cited 40× · PMID 36623804 · DOI 10.1016/j.neuropharm.2023.109418