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   43865   clinical trials with a EudraCT protocol, of which   7286   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:2019-002225-30
    Sponsor's Protocol Code Number:69HCL18_0957
    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:2019-06-05
    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 number2019-002225-30
    A.3Full title of the trial
    Impact of low protein diet supplemented with ketoanalogues on uremic toxins production and glucose metabolism in chronic kidney disease_KETO GUT study
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    Impact of low protein diet supplemented with ketoanalogues on uremic toxins production and glucose metabolism in chronic kidney disease_KETO GUT study
    A.3.2Name or abbreviated title of the trial where available
    KETO-GUT
    A.4.1Sponsor's protocol code number69HCL18_0957
    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 SponsorHospices Civils de Lyon
    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 supportFRESENIUS
    B.4.2CountryFrance
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationHospices Civils de lyon
    B.5.2Functional name of contact pointKarima BRAHAMI
    B.5.3 Address:
    B.5.3.1Street Address3 Quai des Célestins
    B.5.3.2Town/ cityLYON cedex 02
    B.5.3.3Post code69229
    B.5.3.4CountryFrance
    B.5.4Telephone number0033472406883
    B.5.5Fax number0033472115190
    B.5.6E-mailkarima.brahami@chu-lyon.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 ketosteril
    D.2.1.1.2Name of the Marketing Authorisation holderFresenius Kabi France
    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.3.1Product nameketosteril
    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
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    chronic kidney disease
    Insuffisance rénale chronique
    E.1.1.1Medical condition in easily understood language
    chronic kidney disease
    Insuffisance rénale chronique
    E.1.1.2Therapeutic area Diseases [C] - Nutritional and Metabolic Diseases [C18]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10076412
    E.1.2Term Chronic kidney disease stage 5
    E.1.2System Organ Class 100000004857
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10076411
    E.1.2Term Chronic kidney disease stage 4
    E.1.2System Organ Class 100000004857
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    Comparison of the impact of a very low keto-supplement diet (0.4 g / kg / day protein + Ketosteril) in a Chronic kidney disease (CKD) stage 4-5 patient population on plasma accumulation of IS compared to a standard diet (0.8 g / kg / day of protein) after a period of 3 months.
    Comparaison de l’impact d’un régime très pauvre en protéines supplémenté en céto-analogues (0.4 g/kg/jour de protéines + Ketosteril) dans une population de patients IRC de stade 4-5 sur l’accumulation plasmatique de l’IS par rapport à un régime standard (0.8 g/kg/jour de protéines) après une période de 3 mois.
    E.2.2Secondary objectives of the trial
    Comparison of the impact of a very low keto-supplement diet (0.4 g / kg / day protein + Ketosteril) in a CKD stage 4-5 patient population on plasma accumulation of IS compared to a standard diet (0.8 g / kg / day of protein) after a period of 3 months regarding the folowing:

    1-plasma accumulation of other uremic toxins derived from the intestine (PCS and TMAO)

    2-the urinary excretion of TUs derived from the intestine (PCS and IS)

    3- bacterial microbiological profile by sequencing 16s stool samples

    4-insulin secretion and insulin resistance parameters measured during oral glucose tolerance (OGTT).
    5-The secretory profile of digestive hormones (incretins) during an OGTT: GLP-1 and FGF19
    6- Endotoxinemia (LPS)
    7- Concentration and composition of bile acid
    8- Adverse events including malnutrition, digestive disorders, hypophosphatemia and hypercalcemia
    9- Observance of diet
    Comparaison de l’impact d’un régime très pauvre en protéines supplémenté en céto-analogues (0.4 g/kg/jour de protéines + Ketosteril) dans une population de patients IRC de stade 4-5 par rapport à un régime standard (0.8 g/kg/jour de protéines) après une période de 3 mois sur :
    1-l’accumulation plasmatique des autres TUs dérivées de l'intestin (PCS et TMAO)
    2-l’excrétion urinaire des TUs dérivées de l’intestin (PCS et IS)
    3-le profil microbiologique bactérien par séquençage 16s des échantillons de selles
    4-les paramètres d’insulino-sécrétion et insulino-résistance mesurés au cours d’une hyperglycémie provoquée par voie orale (HGPO).
    5-le profil sécrétoire des hormones digestives (incrétines) au cours d’une HGPO : GLP-1 et FGF19
    6-l’endotoxinémie (LPS)
    7-la concentration et la composition des acides biliaires (AB)
    8-les évènements indésirables dont la dénutrition, les troubles digestifs, l’hypophosphorémie et l’hypercalcémie
    9- l’observance du régime
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    - Age between 18 and 80 years
    - CKD stage 4-5 with estimated glomerular filtration rate < 30 ml/min/1,73m2
    - No dialysis
    - No history of kidney transplantation
    - Non-diabetic (fasting glucose <1.26 g / L, or no insulin or oral antidiabetic therapy)
    - BMI between 18 and 30 kg / m²
    - Patient followed in the nephrology department of Professor FOUQUE at the Lyon Sud hospital
    - For women of childbearing age, at least one method of contraception recognized as effective
    - Patient who gave consent to open participation and signed the consent to participate in the study
    - Age compris entre 18 et 80 ans
    - IRC de stades 4-5 soit avec un débit de filtration glomérulaire estimé (DFGe) < 30 ml/min/1,73m2 selon CKD-EPI
    - Non dialysés
    - Pas d’antécédent de transplantation rénale
    - Non diabétique (glycémie à jeun < 1.26 g/L, ou absence de traitement insulinique ou antidiabétique oral)
    - IMC compris entre 18 et 30 kg/m²
    - Patient suivi dans le service de néphrologie du Pr FOUQUE au centre hospitalier Lyon Sud
    - Pour les femmes en âge de procréer, au moins une méthode de contraception reconnue comme efficace
    - Patient ayant donné son consentement de participation libre et ayant signé le consentement de participation à l’étude
    E.4Principal exclusion criteria
    - Patient with progressive inflammatory, infectious, cardiovascular or neoplastic disease
    - Patient refusing a dietary follow-up
    - Patient having a planned transplant or dialysis project in the next 6 months.
    - Patient having a colectomy, resection of the small intestine or cholecystectomy
    - Patient who has received antibiotics, prebiotics, probiotics in the last 3 months.
    - Patient treated with more than 2 g of calcium per day
    - Patient using laxatives (more than 2 per day)
    - Patient having:
    o Uncontrolled metabolic acidosis (bicarbonatemia <18 mM)
    o Hyperparathyroidism (PTH greater than 5 times the upper limit of normal)
    o Hypercalcemia (Calcium> 2.55 mmol / L) or hypophosphoremia <0.70 mmol / L
    o Anemia (hemoglobinemia <80g / L)
    o Undernutrition criteria: albumin <38 g / L or prealbumin <0.3 g / L
    - Known hypersensitivity to any of the substances or excipients of Ketosteril
    - Subject in exclusion period of a previous study
    - Patient not affiliated to social security
    - -atient under guardianship or in the interests of justice
    - Patient who is pregnant, breastfeeding or likely to become pregnant during the study
    - Patient ayant une maladie inflammatoire, infectieuse, cardio-vasculaire ou néoplasique évolutive
    - Patient refusant un suivi diététique
    - Patient ayant un projet de transplantation ou de dialyse prévisible dans les 6 mois à venir.
    - Patient ayant eu une colectomie, une résection de l’intestin grêle ou une cholécystectomie
    - Patient ayant reçu des antibiotiques, prébiotiques, probiotiques dans les 3 derniers mois.
    - Patient traité par plus de 2 g de de calcium par jour
    - Patient utilisant des laxatifs (plus de 2 par jour)
    - Patient ayant :
    o Une acidose métabolique non contrôlée (bicarbonatémie < 18 mM)
    o Une hyperparathyroïdie (PTH supérieure à 5 fois la limite supérieure de la normale)
    o Une hypercalcémie (Calcémie > 2.55 mmol/L) ou hypophosphorémie < 0.70 mmol/L
    o Une anémie (hémoglobinémie < 80g/L)
    o Des critères de dénutrition : albumine< 38 g/L ou préalbumine < 0.3 g/L
    - Hypersensibilité connue à l’une des substances ou à un des excipients du Ketosteril
    - Sujet en période d'exclusion d’une étude précédente
    - Patient non affilié à la sécurité sociale
    - Patient sous tutelle ou en sauvegarde de justice
    - Patiente enceinte, allaitant ou susceptible de tomber enceinte au cours de l’étude
    E.5 End points
    E.5.1Primary end point(s)
    The primary endpoint is the plasma concentration of Indoxyl Sulfate (IS) three months after randomization.
    The plasma concentration of the IS determined by high performance liquid chromatography.
    Le critère de jugement principal est la concentration plasmatique d’Indoxyl Sulfate (IS) trois mois après la randomisation.
    La concentration plasmatique de l’IS déterminée par en chromatographie en phase liquide à haute performance
    E.5.1.1Timepoint(s) of evaluation of this end point
    3 months after randomization
    Trois mois après la randomisation
    E.5.2Secondary end point(s)
    1 ° Evaluation of the plasma concentration of other uremic toxins (PCS and TMAO).
    This analysis will be done on serum that will be collected on the T0 of the OGTT.
    The TAMO assay is done in mass spectroscopy at CRNH de Nantes and the plasma concentration of PCS will be performed in high performance liquid chromatography in the CarMen laboratory, INSA Lyon3,60

    2 ° Assessment of urinary excretion of intestinal uremic toxins (PCS and IS). Urinary concentrations will be performed in high performance liquid chromatography in the CarMen laboratory, INSA Lyon3,60

    3 ° The composition of the microbiota on a stool sample by sequencing 16s of bacterial DNA. The analysis of the microbiota and the statistics will be carried out by the Biomnigene platform.

    4° Measurement of insulin resistance and insulin secretion by: -HbA1C to T0 (assay performed in the usual monitoring) -Glycemia, insulinemia during an OGTT (T0, T15, T30, T60, T90, T120, T180, T240 minutes) to calculate areas under the curve -Formules / index for measuring insulin secretion and insulin resistance. These assays will be performed in the CHLS biochemistry department using routine techniques.

    5 ° Metabolic parameters regulated by bile acids during an OGTT (T0, T15, T30, T60, T90, T120, T180, T240 minutes) -FGF-19 plasma quantified by ELISA method -GLP-1 plasma measured by ELISA method These assays will be performed in the CHLS biochemistry department using routine techniques. An area under the curve during the OGTT will be performed to evaluate the secretion response of FGF19 and GLP1.

    6 ° Measures of endotoxinemia This analysis will be done on serum that will be collected on the T0 of the OGTT. Plasma LPS is measured using the Limulus amoebocyte lysate (LAL) test in the CarMen61 laboratory

    7 ° Assessment of plasma concentration and composition of plasma bile acids. This analysis will be done on serum that will be collected on the T0 of the OGTT. The bile acids will be measured on serum in chromatography (automated technique), the separation is in gas phase for the bile acid composition: cholic acid, chenodeoxycholic, lithocholic. This assay is performed routinely in the CHLS biochemistry department.
    8 ° Unwanted events
    We will determine if this diet can result in particularity:
    - Undernutrition determined by the variation of the weight, parameter of body composition and biochemical (albumin and prealbumin)
    - Hypercalcemia, hypophosphoremia
    - Digestive disorders
    9 ° Observance
    -On the amount of protein estimated by the Maroni formula on urinary urinary urine 24 hours in both groups
    -On the number of tablets taken by the patient and using the treatment intake log in the treated group.
    1° Évaluation de la concentration plasmatique des autres toxines urémiques (PCS et TMAO).
    Cette analyse sera faite sur du sérum qui sera prélevé sur le T0 de l’HGPO.
    Le dosage du TAMO est fait en spectroscopie de masse au CRNH de Nantes et la concentration plasmatique du PCS sera réalisé en chromatographie en phase liquide à haute performance au sein du laboratoire CarMen, INSA Lyon3,60

    2° Évaluation de l’excrétion urinaires des TUs dérivées de l’intestin (PCS et IS).
    Les concentrations urinaires seront réalisées en chromatographie en phase liquide à haute performance au sein du laboratoire CarMen, INSA Lyon3,60

    3° La composition du microbiote sur un échantillon de selles par séquençage 16s de l’ADN bactériens. L’analyse du microbiote et les statistiques seront réalisée par la plateforme Biomnigene.

    4°Mesure de l'insulino-résistance et insulino-sécrétion par :
    -HbA1C à T0 (dosage réalisé dans le suivi habituel)
    -Glycémie, insulinémie au cours d'une HGPO (T0, T15, T30, T60, T90, T120, T180, T240 minutes) pour calculer les aires sous la courbe
    -Formules/index pour mesurer l'insulino-sécrétion et l'insulino-résistance (Annexe n°1)
    Ces dosages seront réalisés dans le service de biochimie du CHLS par les techniques de routines.
    .

    5°Paramètres métaboliques régulés par les acides biliaires au cours d'une HGPO (T0, T15, T30, T60, T90, T120, T180, T240 minutes)
    -FGF-19 plasmatique quantifié par méthode ELISA
    -GLP-1 plasmatique mesuré par méthode ELISA
    Ces dosages seront réalisés dans le service de biochimie du CHLS par des techniques de routines. Une aire sous la courbe durant l’HGPO sera réalisée pour évaluer la réponse de sécrétion du FGF19 et du GLP1.

    6°Mesures de l'endotoxinémie
    Cette analyse sera faite sur du sérum qui sera prélevé sur le T0 de l’HGPO.
    Le LPS plasmatique est mesuré à l’aide du test du lysat d’amœbocyte de limule (LAL) au sein du laboratoire CarMen61.

    7° Évaluation de la concentration plasmatique et composition des acides biliaires plasmatiques.
    Cette analyse sera faite sur du sérum qui sera prélevé sur le T0 de l’HGPO.
    Les acides biliaires seront mesurés sur sérum en chromatographie (technique automatisée), la séparation se fait en phase gazeuse pour la composition en acides biliaires : acide cholique, chenodéoxycholique, lithocholique. Ce dosage est réalisé en routine dans le service de biochimie du CHLS.

    8° Évènements indésirables
    Nous déterminerons si ce régime peut entrainer en particularité :
    - Une dénutrition déterminé par la variation du poids, paramètre de composition corporelle et biochimique ( albumine et préalbumine)
    - Une hypercalcémie, une hypophosphorémie
    - Des troubles digestifs

    9° Observance
    -Sur la quantité de protéines estimée par la formule de Maroni sur l’urée urinaire des urines de 24 h dans les deux groupes
    -Sur le nombre de comprimés prit par le patient et à l’aide du journal de prise de traitement ( Annexe 9)¬ dans le groupe traité.
    E.5.2.1Timepoint(s) of evaluation of this end point
    3 months after randomization
    Trois mois après la randomisation
    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 Yes
    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) 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 Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    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 No
    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.8.5The 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
    Dernière visite du dernier patient inclus
    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 months30
    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: 45
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 40
    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 state85
    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
    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 Decision2019-07-05
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-18
    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-Sat Apr 27 00:57:54 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA