Nitrous Oxide for Late-Life Depression - PROTO-BRAIN

Not Applicable

Recruiting

• Conditions: Resistant Depression, Treatment; Late-Life Depression
• Interventions: Drug: Medical Air; Drug: EMONO

• Registration Number: NCT05007028
• Lead Sponsor: University Hospital, Tours

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).

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 Timeline

• Study First Submitted: 2021-05-27
• Study First Submitted QC: 2021-08-13
• Study First Posted: 2021-08-16
• Study Start: 2021-11-16
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-29
• Last Update Posted: 2024-04-01
• Primary Completion: 2024-12
• Study Completion: 2024-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Medical air	Medical Air	Control Drug: Medical air : 78% N2 / 22% O2
Nitrous Oxide	EMONO	Active Drug: EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide)

Primary Outcome Measures

Name	Time	Method
Change in MADRS	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	montgomery asberg depression scale for symptoms severity

Secondary Outcome Measures

Name	Time	Method
MRI	At Baseline	Structural and Functional MRI
Change in QIDS-SR	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	Quick Inventory of Depressive Symptomatology Self Report, Depression severity
Change in YMRS	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	Young Mania Rating Scale
Change in STAI	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	State-Trait Anxiety Inventory
Change in Clinician Administered Dissociative States Scale	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	CADSS
Change in Brain Tissue Pulsatility	Baseline and immediately after the intervention	Indexes of BTP, including BTP amplitudes
Change in HDRS 17 items	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	Hamilton Depression Rating Scale
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 SSI	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	Scale for Suicidal Ideation
Change in BPRS	Baseline, 2 hours, 24 hours, 1 week, 2 weeks	Brief Psychiatric Rating Scale

Trial Locations

Locations (1)

University Hospital of Tours; 🇫🇷 Tours, France