Using Nitrous Oxide to Treat Late-Life Depression

Nitrous Oxide for Late-Life Depression : a Randomized Controlled Trial With Comparator - PROTO-BRAIN

Not applicable Interventional University Hospital, Tours · NCT05007028

This study is testing if nitrous oxide can help older adults with late-life depression who haven't found relief from regular antidepressants.

Quick facts

PhaseNot applicable
Study typeInterventional
Enrollment60 (estimated)
Ages60 Years to 90 Years
SexAll
SponsorUniversity Hospital, Tours Academic / other
Locations1 site (Tours)
Trial IDNCT05007028 on ClinicalTrials.gov

What this trial studies

This study investigates the efficacy and safety of Nitrous Oxide (N2O) as a treatment for Late-Life Depression (LLD) in older adults who have not responded to traditional antidepressants. Participants aged 60-90 will receive either an equimolar mixture of oxygen and nitrous oxide (EMONO) or medical air, with their depressive symptoms assessed at multiple time points. The study also aims to explore neuroimaging changes associated with treatment response using advanced imaging techniques. By comparing responders and non-responders, the research seeks to provide insights into the potential benefits of N2O for this population.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 60-90 with a major depressive episode who have not responded to at least one prior antidepressant treatment.

Not a fit: Patients with bipolar disorder, schizophrenia, neurodegenerative diseases, or significant unstable medical conditions may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could offer a rapid and effective option for older adults suffering from resistant depression.

How similar studies have performed: While the use of nitrous oxide for midlife depression has shown promise, this specific application for late-life depression is novel and has not been extensively tested.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

* 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

Exclusion Criteria:

* Bipolar disorder, schizophrenic disorder, neurodegenerative disease, documented by the MINI and the MMSE (non-inclusion if MMSE \< 24/30), addictive disorder
* 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
* A person participating in a drug clinical trial or during a period of exclusion from any clinical study

Where this trial is running

Tours

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Late-Life DepressionResistant Depression, TreatmentNitrous OxideMagnetic Resonance ImagingUltrasound Tissue Pulsatility Imaging
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.