DepressionPhase 2PROTO-EHPADNCT06382389
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-
A Phase 2 study testing EMONO and Medical air in people with Depression and Neurocognitive Disorders, run by University Hospital, Tours.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Depression, Neurocognitive Disorders
- What is being tested?
- EMONO and Medical air
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 96 participants
- Where
- No sites listed yet
- Study dates
- Sep 2026to Sep 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
About this study
Official title: 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.
Read the 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.
- Conditions
- Depression, Neurocognitive Disorders
- Being tested
- EMONO, Medical air
- Keywords
- Nitrous Oxide
- Medical subject headings
- Depression, Neurocognitive Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EMONODrug
Also called Nitrous oxide
Exposure of Emono via facial mask
Medical airDrug
Also called comparator
exposure to Medical Air
| Study group | Role | What they receive |
|---|---|---|
| EMONO | Experimental | Equimolar Mixture of Oxygen and Nitrous Oxide (50%O2 / 50%N2O) Active drug: Nitrous Oxide Receives: Drug: EMONO |
| medical air | Active comparator | Comparator : medical Air (78% N2 / 22% O2) Receives: Drug: Medical air |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: baseline, week 4
Secondary outcomes (4)
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
Measured: 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
Measured: 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
Measured: baseline, weeks 1, 2, 3, 4 and 8
Collection of adverse events at all study visits
any adverse events will be collected
Measured: baseline, weeks 1, 2, 3, 4 and 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2024
- Study startSep 2026 (estimated)
- Primary completionSep 2028 (estimated)
- Study completionSep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DepressionStudies of the same condition, open and under way.
- More trials run by University Hospital, ToursThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignement
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 96 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Tours
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06382389
- Sponsor's protocol ID
- DR220204
- Other IDs
- 2023-504691-18-00, 2023
- Acronym
- PROTO-EHPAD
- Status last verified
- Jun 2026
- First submitted
- 19 Apr 2024
- Last updated
- 17 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT06382389
- Acronym / sponsor ID
- PROTO-EHPAD / DR220204
- Conditions
- Depression, Neurocognitive Disorders
- Keywords
- Nitrous Oxide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 96 participants (estimated)
- Lead sponsor
- University Hospital, ToursUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Sep 2028 (estimated)
- Study completion
- Sep 2028 (estimated)
- First posted
- 24 Apr 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel assignement
| Arm | Type | Receives |
|---|---|---|
| EMONO | Experimental | Drug: EMONOEquimolar Mixture of Oxygen and Nitrous Oxide (50%O2 / 50%N2O) Active drug: Nitrous Oxide |
| medical air | Active comparator | Drug: Medical airComparator : medical Air (78% N2 / 22% O2) |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (7 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EMONOAlso: Nitrous oxideExposure of Emono via facial mask | Drug | EMONO |
| Medical airAlso: comparatorexposure to Medical Air | Drug | medical air |
Primary outcome
Changes in the CORNELL depression severitý scale between S4 (one week after the last administration of MEOPA or medical air) and S1 (baseline).
Time frame: baseline, week 4
The CORNELL is a validated scale specifically designed for depression in major neurocognitive disorders
4 secondary outcomes
CORNELL scale and GDS scale at weeks 1, 2, 3, 4 and 8
Time frame: baseline, weeks 1, 2, 3, 4 and 8
CGI-S and CGI-I scales at weeks 1, 2, 3, 4 and 8
Time frame: 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
Time frame: baseline, weeks 1, 2, 3, 4 and 8
Collection of adverse events at all study visits
Time frame: baseline, weeks 1, 2, 3, 4 and 8
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jun 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing EMONO and Medical air in people with Depression and Neurocognitive Disorders, run by University Hospital, Tours.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 17 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in the CORNELL depression severitý scale between S4 (one week after the last administration of MEOPA or medical air) and S1 (baseline). (time frame: baseline, week 4). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jun 2026.