NCT05007028

Brief Summary

Resistant Depression is a common condition in older adults and there is an urgent need for novel antidepressant in this population. Nitrous Oxide (N2O) has recently shown rapid antidepressant effect in midlife depression but no study has currently investigated the efficacy and safety of N2O in Late-Life Depression (LLD), while N2O may prove to be an ideal treatment for LLD because of glutamatergic antagonism and cerebrovascular effects and also a relatively good safety profile. The goal of our study is to compare changes in depressive symptoms after 2 hours, 24 hours, 1 week and 2 week of a 1-hour exposure to EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) versus Medical Air. Secondary Objectives include comparing differences in neuroimaging measures between 3 groups (responders and non-responders in the EMONO group, and patients in the control group).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Nov 2021

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

May 27, 2021

Completed
3 months until next milestone

First Posted

Study publicly available on registry

August 16, 2021

Completed
3 months until next milestone

Study Start

First participant enrolled

November 16, 2021

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 19, 2024

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 19, 2024

Completed
Last Updated

November 24, 2025

Status Verified

November 1, 2025

Enrollment Period

3.1 years

First QC Date

May 27, 2021

Last Update Submit

November 18, 2025

Conditions

Late-Life DepressionResistant Depression, Treatment

Keywords

Nitrous OxideMagnetic Resonance ImagingUltrasound Tissue Pulsatility Imaging

Outcome Measures

Primary Outcomes (1)

  • Change in MADRS

    montgomery asberg depression scale for symptoms severity

    Baseline, 2 hours, 24 hours, 1 week, 2 weeks

Secondary Outcomes (11)

  • Change in Brain Tissue Pulsatility

    Baseline and immediately after the intervention

  • MRI

    At Baseline

  • Change in HDRS 17 items

    Baseline, 2 hours, 24 hours, 1 week, 2 weeks

  • Change in QIDS-SR

    Baseline, 2 hours, 24 hours, 1 week, 2 weeks

  • Change in CGI

    Baseline, 2 hours, 24 hours, 1 week, 2 weeks

  • +6 more secondary outcomes

Study Arms (2)

Nitrous Oxide

EXPERIMENTAL

Active Drug: EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide)

Drug: EMONO

Medical air

PLACEBO COMPARATOR

Control Drug: Medical air : 78% N2 / 22% O2

Drug: Medical Air

Interventions

EMONODRUG

Exposure to 1 hour of EMONO via facial mask

Nitrous Oxide
Medical AirDRUG

Exposure to 1 hour of Medical Air via facial mask

Medical air

Eligibility Criteria

Age60 Years - 90 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Aged 60-90 years-old
  • Major Depressive Episode according to DSM-5 criteria, confirmed by the MINI - Mini International Neuropsychiatric Interview
  • MADRS score greater than 20 (Montgomery Asberg Depression Rating Scale)
  • Patient resistant to at least one well-conducted antidepressant treatment, as documented by the MGH-ATRQ scale
  • Patient who can undergo N2O diffusion via a facial mask
  • Patient who has signed an informed consent
  • Person affiliated with a social security scheme

You may not qualify if:

  • Unstable somatic pathology (including unstable neurological or cardiological diseases at risk of interfering with N2O diffusion)
  • Presence of active and significant psychotic symptoms, at investigator's discretion
  • Contraindications to EMONO (50%N2O/ 50%O2) : pneumothorax, emphysema, bowel obstruction, intracranial hypertension, chronic deficiency in vitamin B12 or B9
  • Contraindications to MRI, including claustrophobia
  • Legal incapacity and/or other circumstances unabling the patient to understand the nature, purpose or consequences of the study

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Tours

Tours, 37044, France

Location

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

Air

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

AtmosphereEnvironmentEcological and Environmental PhenomenaBiological PhenomenaMeteorological ConceptsEnvironment and Public Health

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Randomized double blind trial with comparator
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 27, 2021

First Posted

August 16, 2021

Study Start

November 16, 2021

Primary Completion

December 19, 2024

Study Completion

December 19, 2024

Last Updated

November 24, 2025

Record last verified: 2025-11

Locations

FR(1)