NCT04199143

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

Cerebrovascular Reactivity to Nitrous Oxyde in Resistant Depression: the PROTOBRAIN Pilote Study

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 30 (actual)
• Sponsor: University Hospital, Tours · Academic / Other
• Sex: Female
• Age: 25 Years – 50 Years
• Healthy volunteers: Accepted

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.

Detailed description

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

• Treatment Resistant Depression
• Nitrous Oxyde

Interventions

Type	Name	Description
DRUG	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.
DEVICE	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.
DEVICE	Magnetic Resonance Imaging - MRI	Structural and Functionnal (including BOLD and ASL) MRI will be aquired in this study

Timeline

• Start date: 2020-02-20
• Primary completion: 2021-06-10
• Completion: 2021-06-10
• First posted: 2019-12-13
• Last updated: 2025-12-23

Locations

1 site across 1 country: France