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Nitrous Oxide for Late-Life Depression - PROTO-BRAIN (PROTO-BRAIN)

Primary Purpose

Late-Life Depression, Resistant Depression, Treatment

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
EMONO
Medical Air
Sponsored by
University Hospital, Tours
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Late-Life Depression focused on measuring Nitrous Oxide, Magnetic Resonance Imaging, Ultrasound Tissue Pulsatility Imaging

Eligibility Criteria

60 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Hospital of ToursRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nitrous Oxide

Medical air

Arm Description

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

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

Outcomes

Primary Outcome Measures

Change in MADRS
montgomery asberg depression scale for symptoms severity

Secondary Outcome Measures

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

Full Information

First Posted
May 27, 2021
Last Updated
March 15, 2022
Sponsor
University Hospital, Tours
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1. Study Identification

Unique Protocol Identification Number
NCT05007028
Brief Title
Nitrous Oxide for Late-Life Depression - PROTO-BRAIN
Acronym
PROTO-BRAIN
Official Title
Nitrous Oxide for Late-Life Depression : a Randomized Controlled Trial With Comparator - PROTO-BRAIN
Study Type
Interventional

2. Study Status

Record Verification Date
March 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 16, 2021 (Actual)
Primary Completion Date
July 2023 (Anticipated)
Study Completion Date
July 2023 (Anticipated)

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
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

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized double blind trial with comparator
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Nitrous Oxide
Arm Type
Experimental
Arm Description
Active Drug: EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide)
Arm Title
Medical air
Arm Type
Placebo Comparator
Arm Description
Control Drug: Medical air : 78% N2 / 22% O2
Intervention Type
Drug
Intervention Name(s)
EMONO
Intervention Description
Exposure to 1 hour of EMONO via facial mask
Intervention Type
Drug
Intervention Name(s)
Medical Air
Intervention Description
Exposure to 1 hour of Medical Air via facial mask
Primary Outcome Measure Information:
Title
Change in MADRS
Description
montgomery asberg depression scale for symptoms severity
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Secondary Outcome Measure Information:
Title
Change in Brain Tissue Pulsatility
Description
Indexes of BTP, including BTP amplitudes
Time Frame
Baseline and immediately after the intervention
Title
MRI
Description
Structural and Functional MRI
Time Frame
At Baseline
Title
Change in HDRS 17 items
Description
Hamilton Depression Rating Scale
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in QIDS-SR
Description
Quick Inventory of Depressive Symptomatology Self Report, Depression severity
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in CGI
Description
Clinical Global Impression
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in VAS
Description
Visual Analog Scale for global well-being self assessement
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in STAI
Description
State-Trait Anxiety Inventory
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in SSI
Description
Scale for Suicidal Ideation
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in YMRS
Description
Young Mania Rating Scale
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in Clinician Administered Dissociative States Scale
Description
CADSS
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks
Title
Change in BPRS
Description
Brief Psychiatric Rating Scale
Time Frame
Baseline, 2 hours, 24 hours, 1 week, 2 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Thomas DESMIDT, MD, PhD
Phone
02 34 37 89 52
Ext
+33
Email
t.desmidt@chu-tours.fr
Facility Information:
Facility Name
University Hospital of Tours
City
Tours
ZIP/Postal Code
37044
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Thomas Desmidt, MD, PhD
Phone
02 34 37 89 52
Ext
+33
Email
t.desmidt@chu-tours.fr
First Name & Middle Initial & Last Name & Degree
Thomas DESMIDT, MD, PhD

12. IPD Sharing Statement

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Nitrous Oxide for Late-Life Depression - PROTO-BRAIN

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