Efficacy of EMONO as an add-on Therapy to Conventional Antidepressants for the Treatment of Depressive Symptoms in Nursing-home Residents With Neurocognitive Disorders: a Randomized Controlled Trial- (PROTO-EHPAD)

Efficacy of EMONO as an add-on Therapy to Conventional Antidepressants for the Treatment of Depressive Symptoms in Nursing-home Residents With Neurocognitive Disorders: a Randomized Controlled Trial

Depression in neurocognitive disorders (Alzheimers' disease and related disoders) is a highly prevalent condition, especially in nursing homes. While it is associated with significant distress, the current conventional antidepressants have shown only modest efficacy and exposed to potentially severe side effects.

Recent evidence suggests that nitrous oxide (N2O) in its most commonly used packaging of EMONO (Equimolar Mixture of Oxygen and Nitrous Oxide) has rapid antidepressant properties and a good safety profile. However, no study has investigating the antidepressant effect of EMONO in a population of depressed older adults with moderate to severe neurocognitive disorders in nursing homes.

The principal goal of the PROTO-EHPAD study is to compare the changes in depressive symptoms in such individuals in a randomized controlled trial with a follow up period of 8 weeks, with a dosage escalation procedure.

Study Overview

• Status: Not yet recruiting
• Conditions: Depression; Neurocognitive Disorders
• Intervention / Treatment: Drug: EMONO; Drug: Medical air

Detailed Description

Participants will be exposed to 3 sessions of EMONO (or Medical Air), with intervals of 1 week between sessions : a first session of 20 minutes, a second of 40 minutes one week later and a final session of 60 minutes one week later. Efficacy will be assessed 1 week after each session and 4 weeks after the last session.

• Study Type: Interventional
• Enrollment (Estimated): 96
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Men and women aged 60 and over living in nursing home
• Diagnosis of major neurocognitive disorder according to DSM-V for at least 6 month
• MMSE <= 20/30
• NPI depression >= 4/12
• Patient, family and legal representive consent where applicable Person affiliated to a social security schem

Exclusion Criteria:

• NPI agitation > 6/12
• Unstable somatic pathology (in particular unstable neurological or cardiological pathologies at risk of interfering with the diffusion of MEOPA) and any unexplained recent neurological abnormality.
• Contraindications to the use of MEOPA
• Patients who have already been treated with MEOPA in the 6 months prior to inclusion, for example for painful treatment
• Sub-physiological plasma vitamin B12 or B9 concentration (below the lower limit of the laboratory value).
• A person participating in a clinical drug study or in a period of exclusion from any clinical study due to previous participation
• Personne participant à une étude clinique médicamenteuse ou en période d'exclusion de toute étude clinique du fait d'une précédente participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: EMONO; Equimolar Mixture of Oxygen and Nitrous Oxide (50%O2 / 50%N2O) Active drug: Nitrous Oxide	Drug: EMONO; Exposure of Emono via facial mask; Other Names: Nitrous oxide
Active Comparator: medical air; Comparator : medical Air (78% N2 / 22% O2)	Drug: Medical air; exposure to Medical Air; Other Names: comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in the CORNELL depression severitý scale between S4 (one week after the last administration of MEOPA or medical air) and S1 (baseline).	The CORNELL is a validated scale specifically designed for depression in major neurocognitive disorders	baseline, week 4

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CORNELL scale and GDS scale at weeks 1, 2, 3, 4 and 8	The Geriatric Depression Scale is a self assessed scale for depression in older individuals	baseline, weeks 1, 2, 3, 4 and 8
CGI-S and CGI-I scales at weeks 1, 2, 3, 4 and 8	CGI assesses the clinical global impression of the clinician	baseline, weeks 1, 2, 3, 4 and 8
The measurement of well-being by the EVIBE visual analogue scale at weeks 1, 2, 3, 4, and 8	EVIBE is a visual analog scale specifically designed to measure well being in major cognitive disorders	baseline, weeks 1, 2, 3, 4 and 8
Collection of adverse events at all study visits	any adverse events will be collected	baseline, weeks 1, 2, 3, 4 and 8

Collaborators and Investigators

• Sponsor: University Hospital, Tours

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2024
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026

Study Registration Dates

• First Submitted: April 19, 2024
• First Submitted That Met QC Criteria: April 19, 2024
• First Posted (Actual): April 24, 2024

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Nitrous Oxide
• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Depression; Neurocognitive Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anesthetics, General; Anesthetics; Analgesics, Non-Narcotic; Anesthetics, Inhalation; Nitrous Oxide
• Other Study ID Numbers: DR220204; 2023-504691-18-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No