Nitrous Oxide for Late-Life Depression - PROTO-BRAIN

Sponsor

University Hospital, Tours (Other)

Overall Status

Recruiting

CT.gov ID

NCT05007028

Collaborator

(none)

Enrollment

Location

Arms

19.4

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Resistant Depression is a common condition in older adults and there is an urgent need for novel antidepressant in this population. Nitrous Oxide (N2O) has recently shown rapid antidepressant effect in midlife depression but no study has currently investigated the efficacy and safety of N2O in Late-Life Depression (LLD), while N2O may prove to be an ideal treatment for LLD because of glutamatergic antagonism and cerebrovascular effects and also a relatively good safety profile.

The goal of our study is to compare changes in depressive symptoms after 2 hours, 24 hours, 1 week and 2 week of a 1-hour exposure to EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) versus Medical Air.

Secondary Objectives include comparing differences in neuroimaging measures between 3 groups (responders and non-responders in the EMONO group, and patients in the control group).

Condition or Disease	Intervention/Treatment	Phase
Late-Life Depression Resistant Depression, Treatment	Drug: EMONO Drug: Medical Air	N/A

Detailed Description

Secondary objectives include:

To compare changes in Brain Tissue Pulsatility (BTP) as measured with Ultrasound Tissue Pulsatility Imaging (TPI) between responders in the EMONO group (MADRS change of at least 50%), non-responders in the EMONO group (MADRS change of no more than 50%) and in the Air Medical group
To compare baseline differences in structural (brain volumes, white matter hyperintensities) and functional (resting state connectivity in BOLD, Brain Pulsatility in BOLD, Brain Perfusion in ASL) among the 3 groups
To compare changes in depressive and anxiety symptoms between the active and control group, as assess with Hamilton scale, CGI scale, QIDS-SR, VAS and the STAI scale
To compare safety between the active and control group, as assessed with SSI, YMRS, CADSS, BPRS

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized double blind trial with comparatorRandomized double blind trial with comparator

Masking:

Double (Participant, Investigator)

Primary Purpose:

Treatment

Official Title:

Nitrous Oxide for Late-Life Depression : a Randomized Controlled Trial With Comparator - PROTO-BRAIN

Actual Study Start Date :

Nov 16, 2021

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Jul 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Nitrous Oxide Active Drug: EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide)	Drug: EMONO Exposure to 1 hour of EMONO via facial mask
Placebo Comparator: Medical air Control Drug: Medical air : 78% N2 / 22% O2	Drug: Medical Air Exposure to 1 hour of Medical Air via facial mask

Arm

Intervention/Treatment

Experimental: Nitrous Oxide

Active Drug: EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide)

Drug: EMONO

Exposure to 1 hour of EMONO via facial mask

Placebo Comparator: Medical air

Control Drug: Medical air : 78% N2 / 22% O2

Drug: Medical Air

Exposure to 1 hour of Medical Air via facial mask

Outcome Measures

Primary Outcome Measures

Change in MADRS [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
montgomery asberg depression scale for symptoms severity

Secondary Outcome Measures

Change in Brain Tissue Pulsatility [Baseline and immediately after the intervention]
Indexes of BTP, including BTP amplitudes
MRI [At Baseline]
Structural and Functional MRI
Change in HDRS 17 items [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Hamilton Depression Rating Scale
Change in QIDS-SR [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Quick Inventory of Depressive Symptomatology Self Report, Depression severity
Change in CGI [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Clinical Global Impression
Change in VAS [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Visual Analog Scale for global well-being self assessement
Change in STAI [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
State-Trait Anxiety Inventory
Change in SSI [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Scale for Suicidal Ideation
Change in YMRS [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Young Mania Rating Scale
Change in Clinician Administered Dissociative States Scale [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
CADSS
Change in BPRS [Baseline, 2 hours, 24 hours, 1 week, 2 weeks]
Brief Psychiatric Rating Scale

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Aged 60-90 years-old
Major Depressive Episode according to DSM-5 criteria, confirmed by the MINI - Mini International Neuropsychiatric Interview
MADRS score greater than 20 (Montgomery Asberg Depression Rating Scale)
Patient resistant to at least one well-conducted antidepressant treatment, as documented by the MGH-ATRQ scale
Patient who can undergo N2O diffusion via a facial mask
Patient who has signed an informed consent
Person affiliated with a social security scheme

Exclusion Criteria:

Bipolar disorder, schizophrenic disorder, neurodegenerative disease, documented by the MINI and the MMSE (non-inclusion if MMSE < 24/30), addictive disorder
Unstable somatic pathology (including unstable neurological or cardiological diseases at risk of interfering with N2O diffusion)
Presence of active and significant psychotic symptoms, at investigator's discretion
Contraindications to EMONO (50%N2O/ 50%O2) : pneumothorax, emphysema, bowel obstruction, intracranial hypertension, chronic deficiency in vitamin B12 or B9
Contraindications to MRI, including claustrophobia
Legal incapacity and/or other circumstances unabling the patient to understand the nature, purpose or consequences of the study
A person participating in a drug clinical trial or during a period of exclusion from any clinical study