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"

2023-504691-18-00 Protocol DR220204 Therapeutic exploratory (Phase II) Authorised, recruitment pending

Status Authorised, recruitment pending · 1 EU/EEA countries · 1 sites · Protocol DR220204

Overview

Sponsor-declared trial summary

Phase Therapeutic exploratory (Phase II)
Status Authorised, recruitment pending
Participants planned 96
Countries 1
Sites 1

psychiatry

To compare the changes in depressive symptomatology at 4 weeks after baseline between the MEOPA group and the placebo group (medical air), in a population of nursing-home residents with neurognitive disorders and significant depressive symptoms, resistant to at least one conventional antidepressant

Key facts

Sponsor
Centre Hospitalier Regional Universitaire De Tours
Participant type
Patients
Age range
65+ years
Gender
Male and Female
Therapeutic area
Psychiatry and Psychology [F] - Mental Disorders [F03]
Decision date (initial)
2024-04-03
Transition trial
No
Low-intervention
No
Rare-disease indication
No
Vulnerable population
Yes
Funding sources
DGOS

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the changes in depressive symptomatology at 4 weeks after baseline between the MEOPA group and the placebo group (medical air), in a population of nursing-home residents with neurognitive disorders and significant depressive symptoms, resistant to at least one conventional antidepressant

Secondary objectives 1

  1. Compare changes in baseline depressive symptomatology at 8 weeks between the two groups. 2. Compare changes in baseline clinical global impression at 8 weeks between the two groups 3. Compare changes in baseline psychobehavioural symptoms at 8 weeks between the two groups. 4. To compare changes in perceived well-being from baseline to 8 weeks between the two groups 5. Evaluate the safety profile of MEOPA specific to this use.

Conditions and MedDRA coding

psychiatry

VersionLevelCodeTermSystem organ class
21.1 LLT 10048598 Cognitive disorders 10029205

Study design 10 periods

#TitleAllocationBlindingRoles blindedArms
1 baseline -Préinclusion
A pre-inclusion visit : consent to be signed, verification of inclusion and non-inclusion criteria for patients in EHPAD, and an initial blood sample taken, in particular to ensure that there is no vitamin B9 and B12 deficiency and no supra-physiological plasma homocysteine concentration.
 2 Double [{"id":97429,"code":2,"name":"Investigator"},{"id":97430,"code":1,"name":"Subject"}]
2 baseline -Préinclusion
A pre-inclusion visit : consent to be signed, verification of inclusion and non-inclusion criteria for patients in EHPAD ,and an initial blood sample taken, in particular to ensure that there is no vitamin B9 and B12 deficiency.
 2 Double [{"id":97433,"code":2,"name":"Investigator"},{"id":97432,"code":1,"name":"Subject"}]
3 S1 Viist
The S1 visit will take place a maximum of 7 days later and will include randomisation, administration of the CORNELL, GDS, CGI and NPI scales for baseline values and the first session of MEOPA or medical air lasting 20 minutes.
 Randomised Controlled Double [{"id":97435,"code":2,"name":"Investigator"},{"id":97436,"code":1,"name":"Subject"}] EMONO: MEOPA
Comparator: Comparator
4 S2 Visit
Visit will include a session of MEOPA with a progressive (40 minutes at S2) or medical air. air. The CORNELL, GDS and CGI will be administered before exposure to MEOPA or medical air in order to assess the effectiveness of the previous week's session.
 Randomised Controlled Double [{"id":97438,"code":2,"name":"Investigator"},{"id":97439,"code":1,"name":"Subject"}] EMONO: EMONO
Comparator: Comaprator
5 S3 Visit
Visit will include a session of MEOPA( 60 minutes) or medical air. air. The CORNELL, GDS and CGI will be administered before exposure to MEOPA or medical air in order to assess the effectiveness of the previous week's session.
 Randomised Controlled Double [{"id":97442,"code":1,"name":"Subject"},{"id":97441,"code":2,"name":"Investigator"}] EMONO: EMONO
Comparator: Compartor
6 S4 Viist
S4 visit will allow the CORNELL, GDS, CGI and NPI to be taken one week after the last session. the NPI one week after the last session of MEOPA or medical air, as well as a and a blood sample taken to monitor vitamin B9 and B12.
 Randomised Controlled Double [{"id":97445,"code":2,"name":"Investigator"},{"id":97444,"code":1,"name":"Subject"}] EMONO: EMONO
Comparator: Comparator
7 S8 VIsit
The S8 visit will include the CORNELL, the GDS, the CGI and the NPI to assess remote efficacy
 Randomised Controlled Double [{"id":97448,"code":2,"name":"Investigator"},{"id":97447,"code":1,"name":"Subject"}] EMONO: EMONO
Comparator: Comparator
8 baseline -Préinclusion
A pre-inclusion visit : consent to be signed, verification of inclusion and non-inclusion criteria for patients in EHPAD ,and an initial blood sample taken, in particular to ensure that there is no vitamin B9 and B12 deficiency.
 2 Double [{"id":97450,"code":1,"name":"Subject"},{"id":97451,"code":2,"name":"Investigator"}]
9 baseline -Préinclusion
A pre-inclusion visit : consent to be signed, verification of inclusion and non-inclusion criteria for patients in EHPAD ,and an initial blood sample taken, in particular to ensure that there is no vitamin B9 and B12 deficiency.
 2 Double [{"id":97453,"code":1,"name":"Subject"},{"id":97454,"code":2,"name":"Investigator"}]
10 baseline -Préinclusion
A pre-inclusion visit : consent to be signed, verification of inclusion and non-inclusion criteria for patients in EHPAD ,and an initial blood sample taken, in particular to ensure that there is no vitamin B9 and B12 deficiency.
 2 Double [{"id":97456,"code":1,"name":"Subject"},{"id":97457,"code":2,"name":"Investigator"}]

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

  1. Men and women aged 60 and over living in nursing homes
  2. Diagnosis of major neurocognitive disorder according to DSM-V for at least 6 months
  3. MMSE <= 20/30
  4. NPI depression >= 4/12
  5. Patients resistant to at least one well-tolerated antidepressant as assessed by the MGH-ATRQ scale.
  6. Patient, family and legal representive consent where applicable
  7. Person affiliated to a social security scheme
  8. a person participating in a clinical drug study or in a period of exclusion from any clinical study due to previous participation.

Exclusion criteria 7

  1. NPI agitation > 6/12
  2. 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.
  3. Contraindications to the use of MEOPA
  4. Patients who have already been treated with MEOPA in the 6 months prior to inclusion, for example for painful treatment
  5. Sub-physiological plasma vitamin B12 or B9 concentration (below the lower limit of the laboratory value).
  6. A person participating in a clinical drug study or in a period of exclusion from any clinical study due to previous participation.
  7. Supra-physiological plasma homocysteine concentration (above the upper limit of the analysis laboratory's value)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

  1. Changes in the CORNELL depression severitý scale between S4 (one week after the last administration of MEOPA or medical air) and S1 (baseline).

Secondary endpoints 5

  1. CORNELL scale and GDS scale at weeks 1, 2, 3, 4 and 8
  2. CGI-S and CGI-I scales at weeks 1, 2, 3, 4 and 8
  3. The NPI scale for the frequency and severitý of the 12 most frequent psychobehavioural disorders in TNC at weeks 1, 4 and 8.
  4. The measurement of well-being by the EVIBE visual analogue scale at weeks 1, 2, 3, 4, and 8.
  5. Collection of adverse events at all study visits.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

KALINOX 50%/50%, gaz medicinal comprime

PRD350595 · Product

Active substance
Nitrous Oxide
Pharmaceutical form
MEDICINAL GAS, COMPRESSED
Route of administration
INHALATION
Max daily dose
1 h hour
Max total dose
1 h hour
Max treatment duration
15 Day(s)
Authorisation status
Authorised
ATC code
N01AX63 — -
Marketing authorisation
34009 396 422 4 6
MA holder
AIR LIQUIDE SANTE INTERNATIONAL
MA country
France
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Comparator 1

Medical Air

PRD373551 · Product

Active substance
Nitrogen
Pharmaceutical form
MEDICINAL GAS, COMPRESSED
Route of administration
INHALATION
Max daily dose
1 h hour
Max total dose
8 h hour
Max treatment duration
1 Day(s)
Authorisation status
Authorised
ATC code
V03AN — MEDICAL GASES
Marketing authorisation
PA 0208/009/001
MA holder
BOC GASES IRELAND LTD
MA country
Ireland
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

29 Total trials 17 Recruiting 4 Ended
Academic / Non-commercial
Sponsor organisation
Centre Hospitalier Regional Universitaire De Tours
Address
2 Boulevard Tonnelle
City
Tours
Postcode
37000
Country
France

Scientific contact point

Organisation
Centre Hospitalier Regional Universitaire De Tours
Contact name
Dr NKODO

Public contact point

Organisation
Centre Hospitalier Regional Universitaire De Tours
Contact name
Dr NKODO

Locations

1 EU/EEA country · 1 investigational sites

By country

CountryMS statusPlanned subjectsSites
France Authorised, recruitment pending 96 1
Rest of world — 0 —

Investigational sites

France

1 site · Authorised, recruitment pending
Centre Hospitalier Regional Universitaire De Tours
Tours, 2 Allee Gaston Pages, 37100, Tours

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_ protocol 2023-504691-18-00 1
Protocol (for publication) D1_PROTOCOL_2023-504691-18-00_FP 1.1
Protocol (for publication) D1_PROTOCOL_2023-504691-18-00-FP 2.0
Protocol (for publication) D1_PROTOCOL_with modifications_2023-504691-18-00_FP 1.1
Protocol (for publication) D1_PROTOCOL_with modifications_2023-504691-18-00_FP 2.0
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Comparator 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC KALINOX 1
Summary of Product Characteristics (SmPC) (for publication) G2-smPC Kalinox 2
Synopsis of the protocol (for publication) D1_ Protocol Synopsis 2023-504691-18-00 1
Synopsis of the protocol (for publication) D1_PROTOCOL_Synopsis_2023-504691-18-00 1.1
Synopsis of the protocol (for publication) D1_PROTOCOL_SYNOPSIS_2023-504691-18-00 2.0

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-01-30 France Acceptable
2024-04-03
 2024-04-03
2 SUBSTANTIAL MODIFICATION SM-3 2024-11-22 France Acceptable
2025-01-09
 2025-01-14