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

Primary Purpose

Treatment Resistant Depression, Nitrous Oxyde

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Nitrous Oxide-Oxygen
Tissue Pulsatility Imaging - TPI
Magnetic Resonance Imaging - MRI
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Treatment Resistant Depression focused on measuring Magnetic Resonance Imaging, Ultrasound, Tissue Pulsatility Imaging, Treatment Resistant Depression, Nitrous Oxyde

Eligibility Criteria

25 Years - 50 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • Inclusion criteria common to all participants
  • 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.
  • Inclusion Criteria for Depressive Patients
  • 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.
  • Inclusion criteria for healthy voluntary controls
  • 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.

Sites / Locations

  • University Hospital of Tours

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

healthy voluntary controls

Depressive Patients

Arm Description

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

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

Outcomes

Primary Outcome Measures

Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI
BTP will be measured before, during and after N2O exposure

Secondary Outcome Measures

Brain Volumes (MRI)
White Matter Lesions (MRI)
Resting-State Connectivity (BOLD-MRI)
Brain Pulsatility (BOLD-MRI)
Brain Perfusion in Arterial Spin Labelling (ASL-MRI)
Hamilton scale for depression, 17-items
POMS - Profile of Mood State
QIDS-SR - Quick Inventory of depressive Symptomatology Self Report
CGI - Clinical Global Impressions
STAI-Y-A - State-Trait Anxiety Inventory
subjective VAE- Visual Analog Evaluation
SSI - Scale for Suicidal Ideation
YMRS - Young Mania Rating Scale
CADSS - Clinician administered dissociative States
BPRS - Brief Psychiatric Rating Scale

Full Information

First Posted
December 5, 2019
Last Updated
June 28, 2021
Sponsor
University Hospital, Tours
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1. Study Identification

Unique Protocol Identification Number
NCT04199143
Brief Title
Brain Reactivity to Nitrous Oxyde in Depression : an MRI and Ultrasound Study (PROTOBRAIN Pilote)
Official Title
Cerebrovascular Reactivity to Nitrous Oxyde in Resistant Depression: the PROTOBRAIN Pilote Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
February 20, 2020 (Actual)
Primary Completion Date
June 10, 2021 (Actual)
Study Completion Date
June 10, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Tours

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Treatment Resistant Depression, Nitrous Oxyde
Keywords
Magnetic Resonance Imaging, Ultrasound, Tissue Pulsatility Imaging, Treatment Resistant Depression, Nitrous Oxyde

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
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)
Allocation
Non-Randomized
Enrollment
30 (Actual)

8. Arms, Groups, and Interventions

Arm Title
healthy voluntary controls
Arm Type
Experimental
Arm Description
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
Arm Title
Depressive Patients
Arm Type
Experimental
Arm Description
A single Non-blinded One-hour administration of 50% Nitrous oxyde (N2O) 50%oxygen (O2) Gas Mixture
Intervention Type
Drug
Intervention Name(s)
Nitrous Oxide-Oxygen
Other Intervention Name(s)
KALINOX® 50 %/50 %
Intervention Description
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
Device
Intervention Name(s)
Tissue Pulsatility Imaging - TPI
Intervention Description
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
Intervention Name(s)
Magnetic Resonance Imaging - MRI
Intervention Description
Structural and Functionnal (including BOLD and ASL) MRI will be aquired in this study
Primary Outcome Measure Information:
Title
Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI
Description
BTP will be measured before, during and after N2O exposure
Time Frame
3 months after LVLS
Secondary Outcome Measure Information:
Title
Brain Volumes (MRI)
Time Frame
6 months after LVLS
Title
White Matter Lesions (MRI)
Time Frame
6 months after LVLS
Title
Resting-State Connectivity (BOLD-MRI)
Time Frame
6 months after LVLS
Title
Brain Pulsatility (BOLD-MRI)
Time Frame
6 months after LVLS
Title
Brain Perfusion in Arterial Spin Labelling (ASL-MRI)
Time Frame
6 months after LVLS
Title
Hamilton scale for depression, 17-items
Time Frame
6 months after LVLS
Title
POMS - Profile of Mood State
Time Frame
6 months after LVLS
Title
QIDS-SR - Quick Inventory of depressive Symptomatology Self Report
Time Frame
6 months after LVLS
Title
CGI - Clinical Global Impressions
Time Frame
6 months after LVLS
Title
STAI-Y-A - State-Trait Anxiety Inventory
Time Frame
6 months after LVLS
Title
subjective VAE- Visual Analog Evaluation
Time Frame
6 months after LVLS
Title
SSI - Scale for Suicidal Ideation
Time Frame
6 months after LVLS
Title
YMRS - Young Mania Rating Scale
Time Frame
6 months after LVLS
Title
CADSS - Clinician administered dissociative States
Time Frame
6 months after LVLS
Title
BPRS - Brief Psychiatric Rating Scale
Time Frame
6 months after LVLS

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Inclusion criteria common to all participants 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. Inclusion Criteria for Depressive Patients 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. Inclusion criteria for healthy voluntary controls 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas DESMIDT
Organizational Affiliation
CHRU de TOURS
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Hospital of Tours
City
Tours
ZIP/Postal Code
37044
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

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

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