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   43875   clinical trials with a EudraCT protocol, of which   7295   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:2021-006800-34
    Sponsor's Protocol Code Number:RONIN
    National Competent Authority:Italy - Italian Medicines Agency
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-01-31
    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 ConcernedItaly - Italian Medicines Agency
    A.2EudraCT number2021-006800-34
    A.3Full title of the trial
    The Role of Negr1 In modulating Neuroplasticity in major depression
    Il ruolo di Negr1 nella modulazione della neuroplasticità nella Depressione Maggiore
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Phase IV interventional pharmacological study to identify the changes in neuroplasticity at the cellular, molecular and neural level that occur in patients with major depression following the introduction of drug therapy with venlafaxine.
    Studio interventistico farmacologico di fase IV per identificare i cambiamenti di neuroplasticità a livello cellulare, molecolare e neurale che si verificano nei pazienti con depressione maggiore in seguito all’introduzione della terapia farmacologica con venlafaxina.
    A.3.2Name or abbreviated title of the trial where available
    RONIN
    RONIN
    A.4.1Sponsor's protocol code numberRONIN
    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 SponsorFONDAZIONE IRCCS CA' GRANDA OSPEDALE MAGGIORE POLICLINICO
    B.1.3.4CountryItaly
    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 supportFondazione Cariplo - Bando di ricerca 2019 “Ricerca sulla Sindrome ansioso-depressiva: prevenzione, diagnosi precoce e t
    B.4.2CountryItaly
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationFondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
    B.5.2Functional name of contact pointUOC Psichiatria
    B.5.3 Address:
    B.5.3.1Street AddressVia Francesco Sforza, 35
    B.5.3.2Town/ cityMilano
    B.5.3.3Post code20122
    B.5.3.4CountryItaly
    B.5.4Telephone number0255035934
    B.5.5Fax number0255035952
    B.5.6E-mailalessio.fiorentini@policlinico.mi.it
    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 ZARELIS - 75 MG COMPRESSE A RILASCIO PROLUNGATO 14 COMPRESSE IN BLISTER PVC/PCTFE/AL
    D.2.1.1.2Name of the Marketing Authorisation holderITALFARMACO S.P.A.
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    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.3.1Product nameZARELIS - 75 MG COMPRESSE A RILASCIO PROLUNGATO
    D.3.2Product code [Venlafaxina]
    D.3.4Pharmaceutical form Prolonged-release tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNVENLAFAXINA CLORIDRATO
    D.3.9.1CAS number 99300-78-4
    D.3.9.2Current sponsor codeVenlafaxina
    D.3.9.3Other descriptive nameVenlafaxine
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number75
    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 Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    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
    patients with major depression
    Pazienti affetti da depressione maggiore
    E.1.1.1Medical condition in easily understood language
    Mental disorder
    Disturbo mentale
    E.1.1.2Therapeutic area Psychiatry and Psychology [F] - Mental Disorders [F03]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 21.1
    E.1.2Level PT
    E.1.2Classification code 10057840
    E.1.2Term Major depression
    E.1.2System Organ Class 10037175 - Psychiatric disorders
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate if venlafaxine induces a change in Negr1 gene expression in the whole blood of venlafaxine-treated MDD patients compared to antidepressant-free BD patients experiencing a depressive episode.
    L’obiettivo primario dello studio è quello di valutare se la venlafaxina ha indotto un cambiamento nell'espressione del gene Negr1 nel sangue intero di pazienti con MDD, trattati con venlafaxina, rispetto a pazienti con BD che hanno manifestato un episodio depressivo ma non in trattamento con farmaci antidepressivi.
    E.2.2Secondary objectives of the trial
    - To test the hypothesis that venlafaxine improves resting state brain connectivity in MDD patients through the modulation of Negr1 pathway, compared to venlafaxine-free BD patients
    - To evaluate the variation of molecules able to modulate Negr1 gene expression or participating in Negr1 pathway between BD and MDD groups and within each single group over the follow-up period
    - To identify blood-based and neuroimaging biomarkers of MDD
    - To cross-sectionally assess the correspondence between central (CSF) and peripheral (whole blood) expression levels of Negr1 and related gene within MDD and BD groups at the baseline
    - verificare l'ipotesi che la venlafaxina migliori la connettività cerebrale dello stato di riposo nei pazienti con MDD attraverso la modulazione della via Negr1, rispetto ai pazienti con BD non in trattamento con venlafaxina
    - valutare la variazione di molecole in grado di modulare l'espressione del gene Negr1 o che partecipano alla via di Negr1 tra i gruppi BD e MDD e all'interno di ogni singolo gruppo nel periodo di follow-up
    - Identificare biomarcatori ematici e di neuroimaging di MDD (obiettivo quaternario)
    - Valutare in modo trasversale la corrispondenza tra i livelli di espressione centrale (CSF) e periferico (sangue intero) di Negr1 e del gene correlato all'interno dei gruppi MDD e BD al basale
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    MDD patients (Group 1):
    -age >= 18 and < 65 years old.
    -recent diagnosis of MDD, current depressive episode, as determined by the SCID-CV;
    - clinical indication to switch from ongoing antidepressant therapy to venlafaxine for lack of efficacy and/or tolerance and/or compliance.

    BD patients (Group 2):
    - age >= 18 and < 65 years old.
    -recent diagnosis of BD, current depressive episode, as determined by the SCID-CV;
    -absence of antidepressants in the patient’s pharmacological regimen.

    Healthy controls (Group 3)
    - age >= 18 and < 65 years old.
    - no lifetime diagnosis of psychiatric disorders made following SCID-CV.
    Pazienti affetti da Depressione Maggiore (Gruppo 1):
    - età >= 18 e < 65 anni
    - recente diagnosi di MDD, episodio depressivo in corso, come determinato dalla SCID-CV
    - indicazione clinica al passaggio dalla terapia antidepressiva in corso a venlafaxina per mancanza di efficacia e/o tolleranza e/o compliance

    Pazienti affetti da disturbo bipolare (Gruppo 2):
    - Età >= 18 e < 65 anni
    - recente diagnosi di BD con episodio depressivo attuale, come determinato dalla SCID-CV
    - assenza di antidepressivi nel regime farmacologico del paziente

    Controlli sani (Gruppo 3):
    - età >= 18 e < 65 anni.
    - nessuna diagnosi di disturbi psichiatrici effettuata a seguito di SCID-CV
    E.4Principal exclusion criteria
    MDD patients (Group 1):
    - treatment with venlafaxine ongoing or within 6 months before the recruitment
    -concomitant treatment with an irreversible Mono-Amine Oxidase Inhibitor (I-MAO) or interruption of the IMAO treatment before 14 days from the recruitment;
    -pregnant and breastfeeding woman;
    -Lifetime comorbidity for psychotic disorders, as determined by the SCID-CV;
    -Current, clinically meaningful, substance use disorders;
    -Current comorbidity with neurological conditions or severe head trauma;
    -Neuropsychological diagnosis of intellectual disability;
    -Presence of contraindications to lumbar puncture or MRI
    - known hypersensitivity to the active substance venlafaxine or to any of the excipients
    - Women of Childbearing Potential without a negative pregnancy test and not undertaking a highly effective anticonception treatment at the recruitment

    BD patients (Group 2):
    - Lifetime comorbidity for psychotic disorders, as determined by the SCID-CV;
    -Current, clinically meaningful, substance use disorders;
    -Current comorbidity with neurological conditions or severe head trauma;
    -Neuropsychological diagnosis of intellectual disability;
    -Presence of contraindications to lumbar puncture or MRI.

    Healthy controls (Group 3)
    -Current or previous lifetime therapy with antidepressants
    -Current, clinically meaningful, substance use disorders;
    -Current comorbidity with neurological conditions or severe head trauma;
    -Neuropsychological diagnosis of intellectual disability;
    -Presence of contraindications to MRI scan.
    Pazienti affetti da Depressione Maggiore (Gruppo 1):
    - trattamento con venlafaxina in corso o nei 6 mesi precedenti l’arruolamento;
    -trattamento concomitante con un Inibitore della Mono-Amino Ossidasi (I-MAO) irreversibile o interruzione del trattamento con IMAO prima di 14 giorni dall'arruolamento;
    - donna in gravidanza o in allattamento
    - comorbidità a vita per disturbi psicotici, come determinato dallo SCID-CV;
    - disturbi attuali, clinicamente significativi, legati all’uso di sostanze
    - attuale comorbidità con condizioni neurologiche o trauma cranico grave;
    - diagnosi neuropsicologica di disabilità intellettiva;
    - presenza di controindicazioni all’esecuzione della puntura lombare e della RMN cerebrale
    - nota ipersensibilità al principio attivo venlafaxina o ad uno qualsiasi degli eccipienti
    - Donne in età fertile in assenza di un test di gravidanza negativo e che non stiano assumendo un trattamento anticoncezionale altamente efficace al momento dell’arruolamento

    Pazienti affetti da disturbo bipolare (Gruppo 2):
    - comorbidità a vita per disturbi psicotici, come determinato dallo SCID-CV;
    - disturbi attuali, clinicamente significativi, legati all’uso di sostanze
    - attuale comorbidità con condizioni neurologiche o trauma cranico grave;
    - diagnosi neuropsicologica di disabilità intellettiva;
    - presenza di controindicazioni all’esecuzione della puntura lombare e della RMN cerebrale

    Controlli sani (Gruppo 3):
    - terapia a vita attuale o pregressa con farmaci antidepressivi
    - disturbi attuali, clinicamente significativi, legati all’uso di sostanze
    - attuale comorbidità con condizioni neurologiche o trauma cranico grave;
    - diagnosi neuropsicologica di disabilità intellettiva;
    - presenza di controindicazioni all’esecuzione della RMN cerebrale
    E.5 End points
    E.5.1Primary end point(s)
    To observe a significant (p<0.05 at t student test for continuous variable) differential concentration of Negr1 transcript (mRNA) and protein withing the T0 and T1 (4 weeks) in MDD patients treated with venlafaxine, respect to the antidepressant-free BD patient.
    The differential expression of Negr1 will be calculated for both patients’ groups (MDD and BD) as the absolute variation between the blood Negr1 mRNA and plasmatic protein concentration measured at T0 and T1.
    Osservare una concentrazione differenziale significativa (p<0,05 al test t student per variabile continua) del trascritto Negr1 (mRNA) e della proteina tra T0 e T1 (4 settimane) nei pazienti con MDD trattati con venlafaxina rispetto pazienti BD non in trattamento con farmaci antidepressivi.
    L'espressione differenziale di Negr1 sarà calcolata per entrambi i gruppi di pazienti (MDD e BD) come variazione assoluta tra l'mRNA di Negr1 nel sangue e la concentrazione di proteine plasmatiche misurate a T0 e T1.
    E.5.1.1Timepoint(s) of evaluation of this end point
    4 weeks
    4 settimane
    E.5.2Secondary end point(s)
    - To observe a reorganization of beta-band functional connectivity in EEG-fMRI resting state recordings in MDD patients receiving venlafaxine for 4 weeks, compared to BD patients.
    - To establish a correlation between changes in EEG-FMRI connectivity metrics and Negr1 protein and/or transcript concentration.
    - Quantification of the blood differential concentrations of the ncRNAs BC048612 and miR-203 and of the Negr-1 related proteins Abeta 1-42, tau, P-tau, MAPT, MAP2, GAP43, NCAM, SYP, VEGF, IGF-1, BDNF, FGF-2 for each study group over the follow-up (tertiary endpoint)
    - To compare the differential concentration of the above markers between BD and MDD groups over the follow up period (tertiary endpoint); - To compare peripheral (whole blood) expression levels of Negr1 and related genes as well as
    beta-band functional connectivity from EEG-fMRI between HC, MDD, and BD patients (quaternary endpoint)
    - To quantify levels of Negr1 protein and transcript (mRNA) and of the Negr-1 related proteins Abeta 1-42, tau, P-tau, MAPT, MAP2, GAP43, NCAM, SYP, VEGF, IGF-1, BDNF, FGF-2 in the CSF of BD and MDD subjects at the baseline; (quinary endpoint)
    - To correlate the CSF with the peripheral blood levels of these markers within BD and MDD group; (quinary endpoint)
    - Osservare una riorganizzazione della connettività funzionale della banda beta nelle registrazioni dello stato di riposo EEG-fMRI in pazienti con MDD che ricevono venlafaxina per 4 settimane, rispetto ai pazienti con BD.
    - Stabilire una correlazione tra i cambiamenti nelle metriche di connettività EEG-fMRI e la proteina Negr1 e/o la concentrazione del trascritto.
    - Quantificazione delle concentrazioni ematiche differenziali degli ncRNA BC048612 e miR-203 e delle proteine correlate a Negr-1 Abeta 1-42, tau, P-tau, MAPT, MAP2, GAP43, NCAM, SYP, VEGF, IGF-1, BDNF, FGF-2 per ogni gruppo di studio durante il follow-up (endpoint terziario)
    - Confrontare la concentrazione differenziale dei suddetti marcatori tra i gruppi BD e MDD nel periodo di follow-up (endpoint terziario); - Confrontare i livelli di espressione periferici (sangue intero) di Negr1 e i geni correlati, nonché la connettività funzionale della banda beta attraverso EEG-fMRI tra pazienti HC, MDD e BD (endpoint quaternario)
    - Quantificare i livelli della proteina e del trascritto Negr1 (mRNA) e delle proteine correlate a Negr-1 Abeta 1-42, tau, P-tau, MAPT, MAP2, GAP43, NCAM, SYP, VEGF, IGF-1, BDNF, FGF -2 nel CSF di soggetti con BD e MDD al basale; (endpoint quinario)
    - Correlare il liquido cerebrospinale con i livelli ematici periferici di questi marcatori tra il gruppo BD e MDD; (endpoint quinario)
    E.5.2.1Timepoint(s) of evaluation of this end point
    4 weeks; Baseline (T0)
    4 settimane; basale (T0)
    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 Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    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) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    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 No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Il gruppo controllo è costituito dalla coorte di pazienti con Disturbo Bipolare in episodio depressi
    The control group is represented by the cohort of patients with bipolar disorder currently in depres
    E.8.2.4Number of treatment arms in the trial2
    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.8.4.1Number of sites anticipated in Member State concerned1
    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 Information not present in EudraCT
    E.8.7Trial has a data monitoring committee No
    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
    LVLS
    LVLS
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years2
    E.8.9.1In the Member State concerned months1
    E.8.9.1In the Member State concerned days0
    E.8.9.2In all countries concerned by the trial years2
    E.8.9.2In all countries concerned by the trial months1
    E.8.9.2In all countries concerned by the trial days0
    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 Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers Yes
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    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 No
    F.4 Planned number of subjects to be included
    F.4.1In the member state30
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 30
    F.4.2.2In the whole clinical trial 30
    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)
    After study participation, patients will go on with clinical assessments and treatment as normal clinical practice.
    Al Termine della partecipazione allo studio i pazienti proseguiranno le visite di controllo ed il trattamento secondo la normale pratica clinica.
    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 Decision2022-03-31
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2022-02-08
    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-Fri May 17 13:41:06 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA