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   43874   clinical trials with a EudraCT protocol, of which   7294   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:2021-000152-19
    Sponsor's Protocol Code Number:1
    National Competent Authority:Spain - AEMPS
    Clinical Trial Type:EEA CTA
    Trial Status:Ongoing
    Date on which this record was first entered in the EudraCT database:2022-02-24
    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 ConcernedSpain - AEMPS
    A.2EudraCT number2021-000152-19
    A.3Full title of the trial
    Control strategies and pharmacogenetic study for the personalized treatment of fatty liver associated with metabolic dysfunction in patients with prediabetes.
    Estrategias de control y estudio farmacogenético para el tratamiento personalizado del hígado graso asociado a disfunción metabólica en pacientes con prediabetes.
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    PROMETEO-HG
    PROMETEO-HG
    A.4.1Sponsor's protocol code number1
    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 SponsorConsorcio Centro de Investigación Biomédica en Red, M.P. (CIBER)
    B.1.3.4CountrySpain
    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 supportConsorcio Centro de Investigación Biomédica en Red, M.P. (CIBER)
    B.4.2CountrySpain
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationConsorcio Centro de Investigación Biomédica en Red, M.P. (CIBER)
    B.5.2Functional name of contact pointCIBER
    B.5.3 Address:
    B.5.3.1Street AddressInstituto de Salud Carlos III, Avda. Monforte de Lemos, 3-5 | Pabellón 11
    B.5.3.2Town/ cityMadrid
    B.5.3.3Post code28029
    B.5.3.4CountrySpain
    B.5.6E-mailrebeca.colorado@ciberisciii.es
    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 metformin hydrochloride
    D.2.1.1.2Name of the Marketing Authorisation holderACOFARMA DISTRIBUCION SA
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral 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.IMP: 2
    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 pioglitazone hydrochloride
    D.2.1.1.2Name of the Marketing Authorisation holderLaboratorios Cinfa, S.A.
    D.2.1.2Country which granted the Marketing AuthorisationSpain
    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 Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral 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
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Metabolic Associated Fatty Liver Disease with prediabetes.
    Hígado graso asociado a disfunción metabólica en pacientes con prediabetes.
    E.1.1.1Medical condition in easily understood language
    Metabolic Associated Fatty Liver Disease with prediabetes.
    Hígado graso asociado a disfunción metabólica en pacientes con prediabetes.
    E.1.1.2Therapeutic area Body processes [G] - Metabolic Phenomena [G03]
    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
    To determine which of the three models of therapeutic intervention induces a greater sustained regression of fatty liver associated with long-term metabolic disease (18 months) measured by non-invasive techniques (MRI) in patients with Metabolic Associated Fatty Liver Disease and prediabetes.
    Determinar cuál de los tres modelos de intervención terapéutica induce una mayor regresión mantenida del hígado graso asociado a enfermedad metabólica a largo plazo (18 meses) medida mediante técnicas no invasivas (RNM) en pacientes con HGADM y prediabetes.
    E.2.2Secondary objectives of the trial
    • Investigate whether the variations of the genes involved consistently determine and / or condition the degree of response to dietary treatment with a hypocaloric Mediterranean diet and to drug treatment with metformin and pioglitazone.
    • Explore the changes induced by diet and each pharmacological treatment in the concentration of metabolites derived from mitochondrial function, intestinal microbiota.
    • To determine whether the changes in the concentration of alpha-ketoglutarate and other metabolites derived from the mitochondria induced by the therapeutic intervention models are associated with the progression or regression of fatty liver.
    • Establish which of the three models of therapeutic intervention induces an improvement in the pathogenic factors associated with the development of non-alcoholic fatty liver: peripheral insulin resistance, hepatic insulin resistance, adipose tissue dysfunction, intestinal microbiota.
    • Investigar si las variaciones de los genes implicados determinan y / o condicionan sistemáticamente el grado de respuesta al tratamiento dietético con una dieta mediterránea hipocalórica y al tratamiento farmacológico con metformina y pioglitazona.
    • Explorar los cambios inducidos por la dieta y cada tratamiento farmacológico en la concentración de metabolitos derivados de la función mitocondrial, microbiota intestinal.
    • Determinar si los cambios en la concentración de alfa-cetoglutarato y otros metabolitos derivados de la mitocondria inducidos por los modelos de intervención terapéutica están asociados con la progresión o regresión del hígado graso.
    • Establecer cuál de los tres modelos de intervención terapéutica induce una mejora de los factores patogénicos asociados al desarrollo de hígado graso no alcohólico: resistencia a la insulina periférica, resistencia a la insulina hepática, disfunción del tejido adiposo, microbiota intestinal.
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1. Patients with HGADM according to the clinical criteria of the International Expert Consensus Statement.
    2. Age from 18 to 75 years.
    3. Men and postmenopausal women.
    4. Evidence of significant nonalcoholic fatty liver disease, defined by a proportional attenuation of the intrahepatic signal> 10% observed by magnetic resonance imaging.
    5. Overweight or obese with BMI 25-40 kg / m2
    6. Presence of Prediabetes according to the ADA criteria (fasting blood glucose 100-125 mg / dl or HbA1c 5.7% -6.4% or blood glucose 140-199 mg / dl at 2 hours after SOG).
    1. Pacientes con HGADM según los criterios clínicos del International Expert Consensus Statement.
    2. Edad de 18 a 75 años.
    3. Hombres y mujeres postmenopáusicas.
    4. Evidencia de enfermedad hepática grasa no alcohólica significativa, definida mediante una atenuación proporcional de la señal intrahepática >10% objetivada mediante resonancia nuclear magnética.
    5. Sobrepeso u obesidad con IMC 25-40 kg/m2
    6. Presencia de Prediabetes según los criterios de la ADA (Glucemia en ayunas 100-125 mg/dl o HbA1c 5,7%-6,4% o glucemias 140-199 mg/dl a las 2 horas tras SOG).
    E.4Principal exclusion criteria
    1. Patients with a life expectancy that is less than 5 years.
    2. History of alcohol consumption> 30 g / day in men or> 20 g / day in women for 3 consecutive months in the last year.
    3. Inability to maintain complete alcohol withdrawal during the study period.
    4. Patients with decompensated liver cirrhosis or altered liver function (BiT> 2mg / dL, INR> 1.3).
    5. Treatment with drugs potentially associated with fatty liver disease in the previous 3 months (amiodarone, corticosteroids, methotrexate, tetracyclines, tamoxifen, oral contraceptives).
    6. History of hepatocarcinoma or malignancy in the 5 years prior to inclusion in the study, except cervical carcinoma in situ and basal cell carcinoma or cutaneous basal cell carcinoma.
    7. Being undergoing chemotherapy or radiotherapy treatment.
    8. Other causes of fatty liver: fasting, hemochromatosis, Wilson's disease, or autoimmune hepatitis.
    9. Active evidence of HBV or HCV infection.
    10. Severe heart failure; NYHA functional class III or IV.
    11. Type 1 and 2 diabetes.
    12. Taking other antidiabetic drugs.
    13. Chronic diseases not related to metabolic disease: severe psychiatric, chronic kidney failure (GFR <45 ml / min), chronic respiratory failure, chronic processes necessary for treatment that can modify glucose metabolism.
    14. Severe cardiovascular, renal, endocrine, gastrointestinal, or psychiatric comorbidity that, in the opinion of the investigator, may make adherence to treatment or interpretation of results difficult.
    15. Participants in other clinical trials in the 30 days prior to the start of the study.
    16. Sexually active men with a woman of childbearing age who plans to become pregnant.
    17. Patients with limitation to follow the protocol for any reason.
    1. Pacientes con una expectativa de vida que sea inferior a 5 años.
    2. Historia de consumo de alcohol >30 g/día en hombres o >20 g/día en mujeres durante 3 meses consecutivos en el último año.
    3. Incapacidad para mantener abstinencia etílica completa durante el periodo de estudio.
    4. Pacientes con cirrosis hepática descompensada o con función hepática alterada (BiT>2mg/dL, INR>1,3).
    5. Tratamiento con fármacos potencialmente asociados a enfermedad hepática grasa en los 3 meses previos (amiodarona, corticoides, metotrexato, tetraciclinas, tamoxifeno, anticonceptivos orales).
    6. Historia de hepatocarcinoma o neoplasia maligna en los 5 años anteriores a la inclusión en el estudio, excepto carcinoma de cérvix in situ y de células basales o carcinoma cutáneo basocelular.
    7. Estar en tratamiento quimioterápico o radioterapia.
    8. Otras causas de hígado graso: ayuno, hemocromatosis, enfermedad de Wilson o hepatitis autoinmune.
    9. Evidencia activa de infección VHB o VHC.
    10. Insuficiencia cardíaca severa; clase funcional III o IV de la NYHA.
    11. Diabetes tipo 1 y 2.
    12. Toma de otros fármacos antidiabéticos.
    13. Enfermedades crónicas no relacionadas con la enfermedad metabólica: psiquiátricas severas, insuficiencia renal crónica (FG < 45 ml/min), insuficiencia respiratoria crónica, procesos crónicos necesitados de tratamiento que puedan modificar el metabolismo de la glucosa.
    14. Comorbilidad cardiovascular, renal, endocrina, gastrointestinal o psiquiátrica grave que en opinión del investigador pueda dificultar la adherencia al tratamiento o la interpretación de los resultados.
    15. Participantes en otros ensayos clínicos en los 30 días previos al inicio del estudio.
    16. Varones sexualmente activos con una mujer en edad fértil que planea quedar embarazada.
    17. Pacientes con limitación para seguir el protocolo por cualquier causa.
    E.5 End points
    E.5.1Primary end point(s)
    Significant decrease in the amount of intrahepatic fat (> 20%) in the absence of liver fibrosis progression.
    Disminución significativa de la cantidad de grasa intrahepática (> 20%) en ausencia de progresión de la fibrosis hepática.
    E.5.1.1Timepoint(s) of evaluation of this end point
    Baseline and at 18 months of treatment
    En Viista Basal y a los 18 meses de tratamiento.
    E.5.2Secondary end point(s)
    1- Study of insulin resistance and adipose tissue dysfunction:
    2- Search for non-invasive markers of efficacy of the proposed treatments among circulating metabolites (metabolomic and lipidomic methods).
    3- Study of the intestinal microbiota.
    4- Pharmacogenetic study: influence of genetic variations on the degree of therapeutic response to drugs.
    5- Study of bioimpedanciometry.
    6- Collection of adverse events potentially related to the medication and its administration.
    1- Estudio de la resistencia a la insulina y disfunción del tejido adiposo:
    2- Búsqueda de marcadores no invasivos de eficacia de los tratamientos propuestos entre metabolitos circulantes (métodos metabolómico y lipidómico).
    3- Estudio de la microbiota intestinal.
    4- Estudio farmacogenético: influencia de las variaciones genéticas en el grado de respuesta terapéutica a los fármacos.
    5- Estudio de bioimpedanciometría.
    6- Recolección de eventos adversos potencialmente relacionados con el medicamento y su administración.
    E.5.2.1Timepoint(s) of evaluation of this end point
    1. At Baseline, at 12 months and at 18 months of treatment.
    2. Baseline and at 18 months of treatment.
    3. Baseline and at 18 months of treatment.
    4. Baseline.
    5. Baseline, at 8 months and at 18 months.
    6. From Baseline to 30 days after end of treatment, or study withdrawn.
    1. Visita Basal, a los 12 y 18 meses.
    2. Visita Basal y a los 18 meses de tratamiento.
    3. Visita Basal y a los 18 meses de tratamiento.
    4. Visita Basal.
    5. Visita Basal, a los 8 meses y a los 18 meses de tratamiento.
    6. Desde Visita Basal hasta 30 días después del fin del tratamiento o retirada del estudio.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis Yes
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic Yes
    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) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    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 Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial3
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned6
    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 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
    Última visita del último paciente
    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 months
    E.8.9.1In the Member State concerned days
    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: 293
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 97
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    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 No
    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 state390
    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)
    At the end of the trial, it will be evaluated whether the treatment has been effective or not and the best therapeutic option will be evaluated.
    Al final del ensayo se evaluará si el tratamiento ha sido efectivo o no y se evaluará la mejor opción terapéutica.
    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 Decision2022-02-24
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2021-05-06
    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-Thu May 16 01:18:22 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA