Brain Reactivity to Nitrous Oxyde in Depression : an MRI and Ultrasound Study (PROTOBRAIN Pilote)
Condition: Treatment Resistant Depression; Nitrous Oxyde
MeSH terms: Depression; Depressive Disorder; Depressive Disorder, Treatment-Resistant
Study type: Interventional

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.
    

Intervention name(s): Nitrous Oxide-Oxygen; Tissue Pulsatility Imaging - TPI; Magnetic Resonance Imaging - MRI
Intervention type(s): Drug; Device; Device
Intervention description(s): 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) 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.; Structural and Functionnal (including BOLD and ASL) MRI will be aquired in this study
Other intervention name(s): KALINOX® 50 %/50 %
Intervention MeSH terms: Nitrous Oxide
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Intervention model description: Open-label, Longitudinal, Monocentric, Physiological study comparing depressive patients (responders versus non-respondeurs to Nitrous Oxyde) and healthy volunteers
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Magnetic Resonance Imaging; Ultrasound; Tissue Pulsatility Imaging; Treatment Resistant Depression; Nitrous Oxyde