{
  "abstract": "Introduction In kidney transplantation, immunosuppressive therapy is essential to control alloimmune reactions, prevent graft rejection and improve patient survival rates. However, commonly used drugs like tacrolimus (TAC) and mycophenolate mofetil (MMF) have a narrow therapeutic window and exhibit significant inter- and intra-individual variability in pharmacokinetics (PK) and dose-response relationships. Recent pilot studies suggest that the gut microbiome may influence this variability.Methods and analysis ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA) is a prospective, low-interventional, naturalistic longitudinal trial designed to identify biomarkers of TAC and MMF PK variability by examining gut microbiome changes and modulations after kidney transplantation and their link with TAC and MMF PK. Biological samples from 50 patients will be collected at nine specific timepoints pre- and post-transplantation using a rich PK and biological sampling strategy. This approach will enable the derivation of PK parameters for the investigated drugs and the creation of a biobank for future hypothesis testing.Ethics and dissemination The ENIGMA trial has received ethical approval from the European Medicines Agency (EMA). The reference number of our project is R&D/1325226 and is registered on the Clinical Trial Information System (CTIS) platform with European Union Clinical Trial number 2023–5 08 335-31-00. Results of the trial will be published in scientific journals and presented at different (inter)national conferences.Trial registration number 2023–5 08 335-31-00 EMA.",
  "authors": [
    {
      "affiliations": [
        "Department of Integrated PharmacoMetrics, PharmacoGenetics and PharmacoKinetics Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium",
        "Cellular and Molecular Pharmacology Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium",
        "Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Alice Barbé"
    },
    {
      "affiliations": [
        "Department of Integrated PharmacoMetrics, PharmacoGenetics and PharmacoKinetics Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium",
        "Department of Clinical Chemistry, Cliniques universitaires Saint-Luc, Brussels, Belgium",
        "Louvain Center for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Lidvine Boland"
    },
    {
      "affiliations": [
        "Department of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium",
        "Nephrology Department, Institut de Recherche Experimentale et Clinique, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Nada Kanaan"
    },
    {
      "affiliations": [
        "Surgery and Abdominal Transplant Unit, Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Tom Darius"
    },
    {
      "affiliations": [
        "Surgery and Abdominal Transplant Unit, Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Antoine Buemi"
    },
    {
      "affiliations": [
        "Surgery and Abdominal Transplant Unit, Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Yannick France"
    },
    {
      "affiliations": [
        "Department of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Marie-Agnès Ronsyn"
    },
    {
      "affiliations": [
        "Department of Nephrology, Cliniques universitaires Saint-Luc, Brussels, Belgium"
      ],
      "name": "Sarah Rahal"
    },
    {
      "affiliations": [
        "Department of Integrated PharmacoMetrics, PharmacoGenetics and PharmacoKinetics Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Maxime Lingurski"
    },
    {
      "affiliations": [
        "Cellular and Molecular Pharmacology Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Françoise Van Bambeke"
    },
    {
      "affiliations": [
        "Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium",
        "WELBIO Department, WEL Research Institute, Wavre, Belgium"
      ],
      "name": "Laure B. Bindels"
    },
    {
      "affiliations": [
        "Department of Clinical Chemistry, Cliniques universitaires Saint-Luc, Brussels, Belgium",
        "Louvain Center for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Vincent Haufroid"
    },
    {
      "affiliations": [
        "Nephrology Department, Institut de Recherche Experimentale et Clinique, Université catholique de Louvain, Brussels, Belgium",
        "Surgery and Abdominal Transplant Unit, Cliniques universitaires Saint-Luc, Brussels, Belgium",
        "Department of Nephrology, Cliniques universitaires Saint-Luc, Bruxelles, Belgium"
      ],
      "name": "Arnaud Devresse"
    },
    {
      "affiliations": [
        "Department of Integrated PharmacoMetrics, PharmacoGenetics and PharmacoKinetics Group, Louvain Drug Research Institute, Université catholique de Louvain, Brussels, Belgium",
        "Louvain Center for Toxicology and Applied Pharmacology, Institut de Recherche Expérimentale et Clinique, Université catholique de Louvain, Brussels, Belgium"
      ],
      "name": "Laure Elens"
    }
  ],
  "title": "ElucidatiNg Immunosuppressant pharmacokinetic variabilities by investigating Gut Microbiome modulations After kidney transplantation (ENIGMA): study protocol of a prospective longitudinal trial",
  "uid": "23bdcf51-931f-5a31-8b38-34e5b5af0f3d"
}