Nitrous Oxide for Late-Life Depression - PROTO-BRAIN

Late-Life Depression Clinical Trial

— PROTO-BRAIN  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05007028
• Other study ID #: DR180133
• Secondary ID: 2019-002769-37
• Status: Recruiting
• Phase: N/A
• Start date: November 16, 2021
• Est. completion date: December 2024

Study information

• Verified date: March 2024
• Source: University Hospital, Tours
• Contact: Thomas DESMIDT, MD, PhD
• Phone: 02 34 37 89 52
• Email: t.desmidt[@]chu-tours.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 60 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Treatment-Resistant
• Late-Life Depression

Intervention

Drug:
• EMONO
Exposure to 1 hour of EMONO via facial mask
• Medical Air
Exposure to 1 hour of Medical Air via facial mask

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