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

Treatment Resistant Depression Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04199143
• Other study ID #: DR190058
• Status: Completed
• Phase: N/A
• Start date: February 20, 2020
• Est. completion date: June 10, 2021

Study information

• Verified date: June 2021
• Source: University Hospital, Tours
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 10, 2021
• Est. primary completion date: June 10, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 25 Years to 50 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Nitrous Oxyde
• Treatment Resistant Depression

Intervention

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.
• Magnetic Resonance Imaging - MRI
Structural and Functionnal (including BOLD and ASL) MRI will be aquired in this study

Locations

Country	Name	City	State
France	University Hospital of Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Tours

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Brain Tissue Pulsatility (BTP) as measured with Ultrasound TPI	BTP will be measured before, during and after N2O exposure	3 months after LVLS
Secondary	Brain Volumes (MRI)		6 months after LVLS
Secondary	White Matter Lesions (MRI)		6 months after LVLS
Secondary	Resting-State Connectivity (BOLD-MRI)		6 months after LVLS
Secondary	Brain Pulsatility (BOLD-MRI)		6 months after LVLS
Secondary	Brain Perfusion in Arterial Spin Labelling (ASL-MRI)		6 months after LVLS
Secondary	Hamilton scale for depression, 17-items		6 months after LVLS
Secondary	POMS - Profile of Mood State		6 months after LVLS
Secondary	QIDS-SR - Quick Inventory of depressive Symptomatology Self Report		6 months after LVLS
Secondary	CGI - Clinical Global Impressions		6 months after LVLS
Secondary	STAI-Y-A - State-Trait Anxiety Inventory		6 months after LVLS
Secondary	subjective VAE- Visual Analog Evaluation		6 months after LVLS
Secondary	SSI - Scale for Suicidal Ideation		6 months after LVLS
Secondary	YMRS - Young Mania Rating Scale		6 months after LVLS
Secondary	CADSS - Clinician administered dissociative States		6 months after LVLS
Secondary	BPRS - Brief Psychiatric Rating Scale		6 months after LVLS