Brain Reactivity to Nitrous Oxyde in Depression : an MRI and Ultrasound Study (PROTOBRAIN Pilote)

NCT04199143 | Completed DMC

• 1 other identifier: DR190058
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Recent evidence suggest that Nitrous Oxyde (N2O) could exhibit antidepressant effect in treatment-resistant depression (TRD). However, the pathophysiology of this effect remains unclear and could include glutamatergic activity but also cerebrovascular effects and changes in brain connectivity. The goal of our study is to characterize brain reactivity to N2O in TRD patients, as assessed with Ultrasound Tissue Pulsatility Imaging (TPI) and Magnetic Resonance Imaging (MRI) (including Arterial Spin Labeling - ASL - for brain perfusion and Blood-Oxygen-Level Dependent - BOLD - for brain connectivity and pulsatility). Ultrasound and MRI Neuroimaging will be measured before, during and after a single one-hour exposure of a 50%N20/50%O2 mixture, in depressed individuals (n=20) and healthy volunteers (n=10). We make the hypothesis that brain reactivity will be lower in depressed individuals nonresponders to N2O compared to responders and healthy controls. This study would provide further characterisation of the pathophysiology of the antidepressant response to N2O, as well as providing potential biomakers (Ultrasound and MRI) for treatment response to N2O in TRD.

Conditions

Treatment Resistant Depression; Nitrous Oxyde

Keywords

Magnetic Resonance Imaging; Ultrasound; Tissue Pulsatility Imaging; Treatment Resistant Depression; Nitrous Oxyde

Outcome Measures

Primary Outcomes (1)

• Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI

  BTP will be measured before, during and after N2O exposure

  3 months after LVLS

Secondary Outcomes (15)

• Brain Volumes (MRI)

  6 months after LVLS

• White Matter Lesions (MRI)

  6 months after LVLS

• Resting-State Connectivity (BOLD-MRI)

  6 months after LVLS

• Brain Pulsatility (BOLD-MRI)

  6 months after LVLS

• Brain Perfusion in Arterial Spin Labelling (ASL-MRI)

  6 months after LVLS

Study Arms (2)

healthy voluntary controls

EXPERIMENTAL

A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture

Drug: Nitrous Oxide-Oxygen; Device: Tissue Pulsatility Imaging - TPI; Device: Magnetic Resonance Imaging - MRI

Depressive Patients

EXPERIMENTAL

A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture

Drug: Nitrous Oxide-Oxygen; Device: Tissue Pulsatility Imaging - TPI; Device: Magnetic Resonance Imaging - MRI

Interventions

Nitrous Oxide-Oxygen DRUG

The medical product used in this study is a gas for common medical use in various domains including anesthesic, consisting in the equimolar mixture of nitrous oxide and oxygen. Subjects will receive a mixture of 50% N2O / 50% O2 for 1 hour.

Also known as: KALINOX® 50 %/50 %

Depressive Patients; healthy voluntary controls

Tissue Pulsatility Imaging - TPI DEVICE

Tissue Pulsatility Imaging (TPI) is a variation of ultrasonic Doppler strain imaging we are developing to measure the local expansion and relaxation of the brain tissue over the cardiac cycle to characterize and image perfusion.

Depressive Patients; healthy voluntary controls

Magnetic Resonance Imaging - MRI DEVICE

Structural and Functionnal (including BOLD and ASL) MRI will be aquired in this study

Depressive Patients; healthy voluntary controls

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female between 25 and 50 years of age
• A person who can undergo N2O diffusion via a facial mask.
• A person who has signed an informed consent.
• Person affiliated with a social security scheme.
• Major Depressive Episode according to DSM-5 criteria, confirmed by the MINI - International Neuropsychiatric Interview.
• Patients with an MADRS score greater than 20 (Montgomery
• Asberg Depression Rating Scale).
• Patients resistant to at least one well-conducted antidepressant treatment, as documented by the MGH-ATRQ scale.
• Absence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, schizophrenic disorder, neurodegenerative disease, addiction to one or more toxics documented by the MINI.
• Absence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, schizophrenic disorder, neurodegenerative disease, addiction to one or more toxics documented by the MINI, current or past.

You may not qualify if:

• Unstable somatic pathology (including unstable neurological or cardiological pathologies at risk of interfering with N2O diffusion)
• Presence of active and significant psychotic symptoms, at investigator's discretion
• Contraindications to mixture 50%N2O/ 50%O2: intracranial hypertension, altered state of consciousness, head trauma, pneumothorax, emphysema bubbles, abdominal gaseous distension, administration of less than 3 months of ophthalmic gas (SF6, C3F8,C2F6) used in eye surgery, known and unsubstituted deficiency in vitamin B12 or folic acid, recent and unexplained neurological abnormalities.
• Contraindications to MRI, including claustrophobia.
• Female who is pregnant or breastfeeding or able to procreate without an effective contraceptive method
• Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, purpose or consequences of the study (including major under legal protection).

Sponsors & Collaborators

• University Hospital, Tours: lead

Study Sites (1)

University Hospital of Tours

Tours, 37044, France

Location

Related Publications (1)

• Desmidt T, Dujardin PA, Andersson F, Brizard B, Remenieras JP, Gissot V, Arlicot N, Barantin L, Espitalier F, Belzung C, Tanti A, Robert G, Bulteau S, Gallet Q, Kazour F, Cognet S, Camus V, El-Hage W, Poupin P, Karim HT. Changes in cerebral connectivity and brain tissue pulsations with the antidepressant response to an equimolar mixture of oxygen and nitrous oxide: an MRI and ultrasound study. Mol Psychiatry. 2023 Sep;28(9):3900-3908. doi: 10.1038/s41380-023-02217-6. Epub 2023 Aug 17.

  PMID: 37592013 RESULT

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant

Interventions

kalinox; Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Thomas DESMIDT

  CHRU de TOURS

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Open-label, Longitudinal, Monocentric, Physiological study comparing depressive patients (responders versus non-respondeurs to Nitrous Oxyde) and healthy volunteers

Study Record Dates

• First Submitted: December 5, 2019
• First Posted: December 13, 2019
• Study Start: February 20, 2020
• Primary Completion: June 10, 2021
• Study Completion: June 10, 2021
• Last Updated: December 23, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)