{
  "abstract": "Introduction Lynch syndrome (LS) carriers have a 20–46% lifetime risk of colorectal cancer (CRC) due to mismatch repair gene variants. Mesalamine (5-ASA, 5-aminosalicylic acid), used safely in patients with ulcerative colitis, may reduce CRC risk in LS by decreasing microsatellite instability, a key driver of LS-related cancer. This study evaluates 5-ASA’s efficacy as a tolerable chemopreventive drug, aiming to improve long-term CRC prevention in LS.Methods and analysis This multicentre, multinational, randomised, double-blind, two-arm, phase II clinical study will compare the effects of a 2-year daily intake of 5-ASA (2000 mg) to placebo in LS carriers. The primary objective is to assess whether mesalamine reduces colorectal neoplasia, both benign and malignant, compared with placebo in LS carriers, as detected by colonoscopy at the end of the treatment period (24 months±1 month) and on study completion. Secondary objectives include evaluating whether 5-ASA reduces neoplasia/tumour multiplicity and progression compared with placebo at specified time points, examining variations in the effects of 5-ASA versus placebo based on cancer history, sex and age (<45 years vs ≥45 years), and assessing the safety of 5-ASA in LS carriers.Ethics and dissemination The trial is currently open for enrolment, having received ethical approval from the Regional Ethical Review Board in Stockholm and funding from the Swedish Research Council. The study protocol is the finalised V.10.0 (11 April 2024), transitioned to the European Clinical Trials Information System. LS remains underdiagnosed, which may limit recruitment. The results are of global interest and will be published in peer-reviewed journals and presented at scientific conferences.Trial registration number ClinicalTrials.gov: NCT04920149. EudraCT: 2019-003011-55. EU CT: 2024-514765-19-01.",
  "authors": [
    {
      "affiliations": [
        "Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden",
        "Dept. of Medicine, Ersta Hospital, Stockholm, Sweden"
      ],
      "name": "Ann-Sofie Backman"
    },
    {
      "affiliations": [
        "Dept. of Medicine, Ersta Hospital, Stockholm, Sweden",
        "Department of Medicine, Huddinge, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Alexander Frank"
    },
    {
      "affiliations": [
        "Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark",
        "Copenhagen University Hospital, Copenhagen, Denmark"
      ],
      "name": "Lars Joachim Lindberg"
    },
    {
      "affiliations": [
        "Dept. of Surgery, University of Gothenburg, Gothenburg, Sweden",
        "Sahlgrenska Academy, Gothenburg, Västra Götaland County, Sweden"
      ],
      "name": "David Ljungman"
    },
    {
      "affiliations": [
        "Dept. of Radiation Sciences, Umeå University, Umeå, Sweden",
        "Norrlands University hospital, Uppsala, Austria"
      ],
      "name": "Gustav Silander"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Malmö, Sweden"
      ],
      "name": "Rita J Gustafsson"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Malmö, Sweden"
      ],
      "name": "Tünde Bozsó"
    },
    {
      "affiliations": [
        "Dept. of Medical Sciences, Uppsala University, Uppsala, Sweden",
        "Uppsala University Hospital, Uppsala, Sweden"
      ],
      "name": "Peter T Schmidt"
    },
    {
      "affiliations": [
        "Dept. of Medicine, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Michael Ingre"
    },
    {
      "affiliations": [
        "Medizinische Universitat Wien, Wien, Austria"
      ],
      "name": "Martina Mittlbock"
    },
    {
      "affiliations": [
        "Dept. of Clinical Science and Education, Södersjukhuset, Stockholm, Sweden"
      ],
      "name": "Christian Löwbeer"
    },
    {
      "affiliations": [
        "Lund University, Lund, Sweden",
        "Skåne University Hospital, Malmö, Sweden"
      ],
      "name": "Jan Marsal"
    },
    {
      "affiliations": [
        "Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden"
      ],
      "name": "Annika Lindblom"
    },
    {
      "affiliations": [
        "Dept. of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden",
        "Dept. of Clinical Genetics and Genomics, Karolinska University Hospital, Stockholm, Sweden"
      ],
      "name": "Emma Tham"
    },
    {
      "affiliations": [
        "Clinical Research Department, Copenhagen University Hospital, Kobenhavn, Denmark",
        "Department of Surgical Gastroenterology, Copenhagen University Hospital, Kobenhavn, Denmark"
      ],
      "name": "Christina Therkildsen"
    },
    {
      "affiliations": [
        "Med Univ Vienna, Vienna, UK"
      ],
      "name": "Christoph Gasche"
    },
    {
      "affiliations": [],
      "name": "The International MesaCAPP Study Group"
    }
  ],
  "title": "Mesalamine for Colorectal Cancer Prevention Programme in Lynch syndrome (MesaCAPP): a multicentre, multinational, randomised, two-arm, double-blind, phase II clinical study with mesalamine or placebo in carriers with Lynch syndrome – a study protocol",
  "uid": "0b0e163f-d738-57ac-9e6b-91e58dc76a00"
}