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

NCT ID: NCT04199143

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

30 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-02-20

Study Completion Date

2021-06-10

Brief Summary

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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.

Detailed Description

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Neuroimaging examinations will include:

* Ultrasound Tissue Pulsatility Imaging for assessment of Brain Tissue Pulsatility (BTP) which reflects reactivity in brain movements and mechanical brain properties
* MRI with structural and functional assessments, namely brain volumes, white matter lesions, ASL for brain perfusion and BOLD for resting-state connectivity and brain pulsatility

MRI will be performed before and after a single one-hour exposure of 50%N2O/50%O2 mixture. Ultrasound will be performed before, after and also during gas exposure. Changes in these neuroimaging parameters will constitute the primary assessment of the study. Psychometric and safety assessements will complete the neuroimaging outcomes.

Follow-up will includes 1) a baseline visit for baseline MRI and Psychometric assessements, 2) a second visit for gas exposure and neuroimaging assessements, 3) a third and fourth visits for psychometric and safety assessements, respectively 24 hours and one week after gas exposure.

Conditions

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Treatment Resistant Depression Nitrous Oxyde

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Open-label, Longitudinal, Monocentric, Physiological study comparing depressive patients (responders versus non-respondeurs to Nitrous Oxyde) and healthy volunteers
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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healthy voluntary controls

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

Group Type EXPERIMENTAL

Nitrous Oxide-Oxygen

Intervention Type 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.

Tissue Pulsatility Imaging - TPI

Intervention Type 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.

Magnetic Resonance Imaging - MRI

Intervention Type DEVICE

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

Depressive Patients

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

Group Type EXPERIMENTAL

Nitrous Oxide-Oxygen

Intervention Type 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.

Tissue Pulsatility Imaging - TPI

Intervention Type 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.

Magnetic Resonance Imaging - MRI

Intervention Type DEVICE

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

Interventions

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Nitrous Oxide-Oxygen

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.

Intervention Type DRUG

Tissue Pulsatility Imaging - TPI

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.

Intervention Type DEVICE

Magnetic Resonance Imaging - MRI

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

Intervention Type DEVICE

Other Intervention Names

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KALINOX® 50 %/50 %

Eligibility Criteria

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Inclusion Criteria

* 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.

Exclusion Criteria

* 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).
* A person participating in a drug clinical trial or during a period of exclusion from any clinical study due to previous involvement.
Minimum Eligible Age

25 Years

Maximum Eligible Age

50 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

Yes

Sponsors

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University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Thomas DESMIDT

Role: PRINCIPAL_INVESTIGATOR

CHRU de TOURS

Locations

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University Hospital of Tours

Tours, , France

Site Status

Countries

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France

References

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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.

Reference Type RESULT
PMID: 37592013 (View on PubMed)

Other Identifiers

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DR190058

Identifier Type: -

Identifier Source: org_study_id