Nitrous Oxide in Resistant Depression in Elderly Subjects: A Randomized, Double-blind, Comparator Trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Regional Universitaire De Tours

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

16 Nov 2021 → 19 Dec 2024

Decision date (initial)

2024-11-12

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-517549-15-00

EudraCT number

2019-004984-31

ClinicalTrials.gov

NCT05007028

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Pharmacodynamic, Safety, Efficacy

To compare changes in depressive symptomatology at 2 hours, 24 hours, Week 1 and Week 2 of exposure to MEOPA versus medical air, in a population of elderly subjects with a characterized depressive episode meeting the criteria for resistant depression and treated with antidepressants.

Secondary objectives 4

1. To compare the dynamics of changes in Tissue Pulsatility Imaging (TPI) during diffusion of the gaseous product between responder (MADRS decrease > 50%), non-responder (MADRS decrease < 50%) and comparator patients
2. To compare structural (brain volume, brain leukopathy) and functional (ASL infusion, BOLD Pulsatility and Brain Connectivity) MRI data between responder, non-responder and comparator patients at baseline
3. To compare changes in depressive symptomatology between subjects in the MEOPA group vs. the comparator group, as measured by the Hamilton scales for intensity of depressive symptoms, CGI for change in global clinical impression, QIDS-SR for self-report of mood, STAI-Y-A for anxiety symptoms and subjective VAS for general state of health
4. To compare tolerance between subjects in the MEOPA group vs. comparator group, as measured by the SSI scale for suicidal ideation, YMRS for manic symptoms, CADSS and BPRS for dissociative symptoms

Conditions and MedDRA coding

Resistant Depression in the Elderly Subject

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Between 60 and 90 years old
2. Diagnosis of depressive episode characterized according to DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI)
3. Depression score on the MADRS scale greater than 20 (Montgomery Asberg Depression Rating Scale)
4. Patients resistant to at least one well-conducted antidepressant for the current depressive episode as assessed by the MGH-ATRQ scale
5. Patients who can be subjected to the delivery of MOEPA via a facial mask
6. A person who has signed an informed consent form
7. Person affiliated with a social security or other regime

Exclusion criteria 7

1. Bipolar disorder, schizophrenic, neurodegenerative disease documented by MINI and MMSE (non-inclusion if MMSE< 24/30), addiction to one or more toxic substances
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. Presence of active and significant psychotic symptoms, at the discretion of the investigator
4. Contraindications to the use of MEOPA and any condition where air is trapped́ inside the body and its expansion could be dangerous: Pneumothorax, emphysema, intestinal obstruction, intracranial hypertension, known and unsubstituted vitamin B12 or B9 deficiency (based on a dosage less than 1 month old), Patients requiring oxygen ventilation; Any alteration in the state of consciousness, preventing patient cooperation; Head trauma; Gas embolism; Diving accident; Abdominal gas distension; Patient who has recently received an ophthalmic gas (SF6, C3F8, C2F6) used in eye surgery (as long as a gas bubble persists inside the eye and for at least 3 months)
5. Contraindications to MRI, including claustrophobia, a metallic foreign body in the eye, pacemaker, neurostimulator, cochlear implants (or non-removable electronic medical equipment), old-generation heart valves, vascular clips formerly implanted on a cranial aneurysm
6. Legal incapacity and/or other circumstances rendering the patient incapable of understanding the nature, objective or consequences of the study
7. Person taking part in a clinical drug study or in a period of exclusion from any clinical study due to previous participation

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. MADRS Depression Severity Scale collected collected at baseline, 2 hours, 24 hours, Week 1 and Week 2 in MEOPA vs comparator group

Secondary endpoints 4

1. Brain Pulsatility Indices as measured by IPT Ultrasound Imaging
2. Brain volume and white matter lesion indices measured by MRI, indicators of brain atrophy and lesion load; Brain perfusion indices measured by MRI-ASL; Pulsatilité́ and Brain Connectivity indices as measured by MRI in BOLD signal
3. A series of scales complementary to the MADRS for the evolution of depressive symptoms (Hamilton 17-items, CGI - Clinical Global Impression, QIDS-SR - Quick Inventory of Depressive Symptomatology Self Report)
4. A series of scales for the evaluation of possible adverse effects (SSI - Scale for Suicidal Ideation, YMRS - Young Mania Rating Scale, CADSS - Clinician Administered Dissociative States Scale, BPRS - Brief Psychiatric Rating Scale)

Investigational products

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

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Regional Universitaire De Tours

Sponsor organisation

Centre Hospitalier Regional Universitaire De Tours

Address

2 Boulevard Tonnelle

City

Tours Cedex 9

Postcode

37044

Country

France

Scientific contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Thomas DESMIDT

Public contact point

Organisation

Centre Hospitalier Regional Universitaire De Tours

Contact name

Thomas DESMIDT

Locations

1 EU/EEA country · 4 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 10 files

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

Application history

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