Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43871   clinical trials with a EudraCT protocol, of which   7290   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-002769-37
    Sponsor's Protocol Code Number:DR190058
    National Competent Authority:France - ANSM
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2019-07-15
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedFrance - ANSM
    A.2EudraCT number2019-002769-37
    A.3Full title of the trial
    Cerebrovascular reaction to nitrous oxide in Resistant Depression: Pilot study (PROTO-BRAIN)
    Réactivité Cérébrovasculaire au Protoxyde d’Azote dans la Dépression Résistante : Etude pilote (PROTO-BRAIN)
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Cerebrovascular reaction to nitrous oxide in Resistant Depression: Pilot study (PROTO-BRAIN)
    Réactivité Cérébrovasculaire au Protoxyde d’Azote dans la Dépression Résistante : Etude pilote (PROTO-BRAIN)
    A.3.2Name or abbreviated title of the trial where available
    PROTO-BRAIN pilot
    PROTO-BRAIN pilote
    A.4.1Sponsor's protocol code numberDR190058
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCHRU DE TOURS
    B.1.3.4CountryFrance
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportFondation "de l'AVENIR"
    B.4.2CountryFrance
    B.4.1Name of organisation providing supportFondation pour l'étude du cerveau "Thérèse et René PLANIOL"
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCHRU DE TOURS
    B.5.2Functional name of contact pointClinical Reasearch Associate
    B.5.3 Address:
    B.5.3.1Street Address2 Boulevard Tonnellé
    B.5.3.2Town/ cityTOURS
    B.5.3.3Post code37044
    B.5.3.4CountryFrance
    B.5.4Telephone number0033218370824
    B.5.5Fax number0033247473876
    B.5.6E-mailcicit@chu-tours.fr
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name KALINOX®
    D.2.1.1.2Name of the Marketing Authorisation holderAir Liquide Santé International
    D.2.1.2Country which granted the Marketing AuthorisationFrance
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Medicinal gas, compressed
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPInhalation use
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Resistant Depression - Nervous Breakdown
    Dépression Résistante
    E.1.1.1Medical condition in easily understood language
    Resistant Depression - Nervous Breakdown
    Dépression Résistante
    E.1.1.2Therapeutic area Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Investigative Techniques [E05]
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Compare measurements of cerebral pulsatility in Ultrasound (Tissue pulsatility Imaging – TPI) before, during and after N2O diffusion, between responders ( decrease of MADRS≥ 50%), non-responders (decrease of MADRS < 50%) and healthy volunteers.
    Comparer les mesures de la Pulsatilité Cérébrale en Ultrasons (Tissue Pulsatility Imaging – TPI) avant, pendant et après la diffusion du N2O, entre patients répondeurs (baisse de la MADRS ≥ 50%), non-répondeurs (baisse de la MADRS < 50%) et sujets volontaires sains.
    E.2.2Secondary objectives of the trial
    1. Compare the dynamics of changes before and after exposure to N2O, cerebral pulsatility measured in MRI-BOLD, cerebral infusion measured by MRI-ASL and resting functional connectivity measured by MRI-BOLD between responders, non-responders and healthy volunteers.

    2. Compare changes in depressive symptomatology in the depressive group, before and after treatment with N2O, as measured by the Hamilton scales, POMS for rapid mood changes, QIDS-SR for mood self-assessment, CGI, STAI-Y-A, EVA subjective.

    3. Assess tolerance in all study participants after N2O treatment, as measured by SSI scales for suicidal ideations, YMRS for manic symptoms, CADSS
    1. Comparer la dynamique de changements avant et après exposition au N2O, de la pulsatilité cérébrale mesurée en IRM-BOLD, de la perfusion cérébrale mesurée par IRM-ASL et de la connectivité fonctionnelle de repos mesurée par IRM-BOLD entre patients répondeurs, non-répondeurs et sujets volontaires sains.

    2. Comparer les changements de symptomatologie dépressive dans le groupe des sujets dépressifs, avant et après traitement par N2O, telle que mesurée par les échelles d’Hamilton, POMS pour les changements rapides d’humeur, QIDS-SR pour auto-évaluation de l’humeur, CGI, STAI-Y-A, EVA subjective.

    3. Evaluer la tolérance chez tous les participants de l’étude, après traitement par N2O, mesurée notamment par les échelles SSI pour les idéations suicidaires, YMRS pour les symptômes maniaques, CADSS et BPRS pour les symptômes dissociatifs et effets secondaires (prise-M).
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Inclusion criteria common to all participants
    o Female between 25 and 50 years of age.
    o A person who can undergo N2O diffusion via a facial mask.
    o A person who has signed an informed consent.
    o Person affiliated with a social security scheme.

    Inclusion Criteria for Depressive Patients
    o Depressive episode diagnosis characterized according to DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI).
    o Patients with an ASRD depression score greater than 20 (Montgomery Asberg Depression Rating Scale).
    o Patients resistant to at least one well-conducted antidepressant treatment, as documented by the MGH-ATRQ scale.
    o Absence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, addiction toAbsence of: bipolar disorder, schizophrenic disorder, neurodegenerative disease, addiction to one or more toxics documented by the MINI.

    Inclusion criteria for healthy voluntary controls
    o Absence of: clinically significant psychiatric disorders, depression, bipolar disorder, schizophrenia or neurodegenerative disease, current or past.
    Critères d’inclusion communs à toutes les personnes participantes
    o Femme entre 25 et 50 ans.
    o Personne pouvant se soumettre à la diffusion de N2O via un masque facial.
    o Personne ayant signé un consentement éclairé.
    o Personne affiliée à un régime de sécurité sociale.

    Critères d’inclusion pour les patients dépressifs
    o Diagnostic d’épisode dépressif caractérisé selon les critères duDSM-5, confirmé par le Mini International Neuropsychiatric Interview (MINI).
    o Patients présentant un score de dépression à l’échelle MADRS supérieur à 20 (Montgomery Asberg Depression Rating Scale).
    o Patients résistant à au moins un traitement antidépresseur bien conduit, tel que documenté par l’échelle MGH-ATRQ.
    o Absence de : trouble bipolaire, schizophrénique, maladie neurodégénérative, addiction à un ou plusieurs toxiques documentés par le MINI.

    Critères d’inclusion pour les sujets contrôles volontaires sains
    o Absence de : troubles psychiatriques connus cliniquement significatifs, dépression, trouble bipolaire, schizophrénique ou maladie neurodégénérative, actuels ou passés.
    E.4Principal exclusion criteria
    o Unstable somatic pathology (including unstable neurological or cardiological pathologies at risk of interfering with N2O diffusion)

    o Presence of active and significant psychotic symptoms, at investigator’s discretion

    o Contraindications to mixture 50%N2O/ 50%O2: intracranial hypertension, altered state of consciousness, head trauma, pneumothorax, emphysema bubbles, abdominal gaseous distension, administration of less than 3 months of ophthalmic gas (SF6, C3F8, C2F6) used in eye surgery, known and unsubstituted deficiency in vitamin B12 or folic acid, recent and unexplained neurological abnormalities.

    o Contraindications to MRI, including claustrophobia.
    Female who is pregnant or breastfeeding or able to procreate without an effective contraceptive method

    o Legal incapacity and/or other circumstances rendering the patient unable to understand the nature, purpose or consequences of the study (including major under legal protection).

    o A person participating in a drug clinical trial or during a period of exclusion from any clinical study due to previous involvement.
    o Pathologie somatique instable (notamment pathologies neurologiques ou cardiologiques instables à risque d’interférer avec la diffusion du N2O)

    o Présences de symptômes psychotiques actifs et significatifs, à la discrétion de l’investigateur

    o Contre-indications au mélange 50%N2O / 50%O2 : hypertension intracrânienne, altération de l’état de conscience, traumatisme crânien, pneumothorax, bulles d’emphysème, distension gazeuse abdominale, administration de moins de 3 mois de gaz ophtalmiques (SF6, C3F8, C2F6) utilisés dans la chirurgie oculaire, déficit connu et non substitué en vitamine B12 ou en acide folique, anomalies neurologiques de survenue récente et non expliquées.

    o Contre-indications à l’IRM, notamment claustrophobie.

    o Femme enceinte ou en période d’allaitement ou en capacité de procréer sans méthode contraceptive efficace

    o Incapacité légale et/ou autre circonstance rendant le patient incapable de comprendre la nature, l’objectif ou les conséquences de l’étude (dont majeur sous protection juridique).

    o Personne participant à une étude clinique médicamenteuse ou en période d’exclusion de toute étude clinique du fait d’une précédente participation.
    E.5 End points
    E.5.1Primary end point(s)
    Cerebral pulsatility indices as measured by TPI ultrasonic imaging
    Indices de Pulsatilité Cérébrale tels que mesurés par l’imagerie Ultrasonore de la TPI
    E.5.1.1Timepoint(s) of evaluation of this end point
    2 months after LVLS
    2 mois après la DVDP
    E.5.2Secondary end point(s)
    Brain pulsatility indices measured by MRI-BOLD; Brain infusion indices measured by MRI-ASL; Brain connectivity indices of 3 neural networks (default mode, cognitive and emotional control network) as measured by the MRI in BOLD signal

    2. A series of scales complementary to the MADRS for the evolution of depressive symptoms (Hamilton 17-items, POMS – Profile of Mood State, QIDS-SR – Quick Inventory of depressive Symptomatology Self Report, CGI – Clinical Global Impressions, STAI-Y-A – State-Trait Anxiety Inventory, EVA subjective – Visual Analog Evaluation)

    3. A series of scales for assessing potential adverse reactions (SSI – Scale for Suicidal Ideation, YMRS – Young Mania Rating Scale, CADSS – Clinician administered dissociative States, BPRS – Brief Psychiatric Rating Scale ; prise-M).
    1. Indices de pulsatilité cérébrale mesurés par IRM-BOLD ; Indices de perfusion cérébrale mesurés par IRM-ASL ; Indices de connectivité cérébrale de 3 réseaux neuronaux (réseau du mode par défaut, du contrôle cognitif et affectif) tels que mesurés par l'IRM en signal BOLD

    2. Une série d’échelles complémentaires à la MADRS pour l’évolution des symptômes dépressifs (Hamilton 17-items, POMS – Profile of Mood State, QIDS-SR – Quick Inventory of Depressive Symptomatology Self Report, CGI – Clinical Global Impressions, STAI-Y-A – State-Trait Anxiety Inventory, EVA subjective – Evaluation Visuelle Analogique)

    3. Une série d’échelles pour l’évaluation des effets indésirables éventuels (SSI – Scale for Suicidal Ideation, YMRS – Young Mania Rating Scale, CADSS – Clinician Administered Dissociative States Scale, BPRS – Brief Psychiatric Rating Scale ; prise-M).
    E.5.2.1Timepoint(s) of evaluation of this end point
    maximum of 6 month post the last visit of last subject
    6 mois maximum après la dernière visite du dernier patient
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety No
    E.6.5Efficacy No
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic Yes
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others Yes
    E.6.13.1Other scope of the trial description
    neuro-imaging
    neuro-imagerie
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) Yes
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled No
    E.8.1.1Randomised No
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other Yes
    E.8.1.7.1Other trial design description
    Longitudinale
    Longitudinal
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other No
    E.8.3 The trial involves single site in the Member State concerned Yes
    E.8.4 The trial involves multiple sites in the Member State concerned No
    E.8.5The trial involves multiple Member States No
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVSLS
    DVDP
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years
    E.8.9.1In the Member State concerned months18
    E.8.9.1In the Member State concerned days17
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) Yes
    F.1.2.1Number of subjects for this age range: 30
    F.1.3Elderly (>=65 years) No
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male No
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others Yes
    F.3.3.7.1Details of other specific vulnerable populations
    female adult of 25-50 years
    femme entre 25 et 50 ans
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    None
    Pas de traitement prévu post essai
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-08-23
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-11-13
    P. End of Trial
    P.End of Trial StatusOngoing
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sun May 05 11:52:58 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA