mSEPT9 Biomarker for Predicting Hepatocellular Carcinoma Occurrence in Patients With Cirrhosis

Официальное название

Evaluation of the Circulating Epigenetic Biomarker mSEPT9 for Predicting the Occurrence of Hepatocellular Carcinoma in Patients With Cirrhosis: A Prospective Multicenter Trial (SEPT9_SuRV)

Обзор

This study aims to evaluate the role of the circulating epigenetic biomarker mSEPT9 in predicting the risk of hepatocellular carcinoma (HCC) in patients with cirrhosis. HCC is a primary liver cancer that frequently develops in individuals with cirrhosis, and early detection is critical for improving outcomes. This research involves 400 patients with cirrhosis who will be followed every six months for up to 60 months. During these visits, blood samples will be collected to analyze mSEPT9 levels. By identifying changes in this biomarker, the study seeks to improve early diagnosis and personalize surveillance strategies, potentially enhancing patient survival and quality of life.

Подробное описание

This study is a prospective, multicenter cohort trial designed to assess the prognostic utility of the circulating epigenetic biomarker mSEPT9 in predicting the development of hepatocellular carcinoma (HCC) among patients with cirrhosis. The trial involves 400 participants who are confirmed to have cirrhosis and no evidence of HCC at baseline.

The study's primary focus is to evaluate the association between a "switch" in the mSEPT9 test-from a triple-negative status (no methylation detected across triplicate assays) to at least one positive triplicate-and the subsequent occurrence of HCC. Secondary objectives include assessing this association across different etiologies of cirrhosis (e.g., viral hepatitis, alcohol-related liver disease, nonalcoholic steatohepatitis) and its correlation with HCC-related mortality.

Participants will undergo standardized clinical, biological, and imaging assessments every six months over a follow-up period of 60 months, as per international guidelines for cirrhosis management. In addition to routine care, blood samples will be collected at each visit for mSEPT9 testing. These samples will be processed, stored at -80°C, and analyzed in batches to assess mSEPT9 levels.

The findings from this study are expected to address the unmet need for reliable, non-invasive biomarkers for HCC risk prediction, potentially leading to personalized surveillance strategies and earlier intervention for patients with cirrhosis. Data will be managed using an electronic case report form (eCRF) to ensure secure, standardized documentation across all participating centers. Results from mSEPT9 testing will not influence clinical management during the study period but will be analyzed to determine their predictive value for HCC development and prognosis.

Вмешательства

• Диагностический тест Circulating mSEPT9 Biomarker Testing
  This intervention involves the analysis of the circulating epigenetic biomarker mSEPT9 through plasma samples collected from patients with cirrhosis. The mSEPT9 test evaluates the methylation status of the SEPT9 gene promoter using a triplicate assay. A "switch" in the test status, defined as a transition from triple-negative (no methylation detected in any triplicate) to at least one positive triplicate, is being investigated as a prognostic marker for the development of hepatocellular carcinom

Первичные конечные точки

• Association Between mSEPT9 Test Switch and Hepatocellular Carcinoma (HCC) Development [Срок оценки: Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.]

Вторичные конечные точки (3)

• Association Between mSEPT9 Test Switch and HCC Development by Cirrhosis Etiology [Срок оценки: Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.]
• Association Between mSEPT9 Test Results and HCC-Related Mortality [Срок оценки: Annually for up to 60 months or until HCC-specific death occurs.]
• Establishment of a Biobank for Genomic and Epigenomic Analysis [Срок оценки: For each participant, samples will be collected at enrollment (baseline) and during follow-up visits every 6 months for up to 60 months.]

Критерии участия

Критерии включения

• Adults aged 18 years or older.
• Patients diagnosed with cirrhosis confirmed by clinical, biochemical, radiological, or histological criteria.
• Cirrhosis attributable to one or more of the following etiologies: alcohol, hepatitis C (HCV), hepatitis B (HBV), nonalcoholic steatohepatitis (NASH), hemochromatosis, autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis, or cryptogenic causes.
• Patients actively followed in one of the participating study centers.
• Patients affiliated with a social security program or equivalent.
• Patients with a body weight greater than 45 kg.
• Patients who have been fully informed about the study procedures and have provided oral informed consent.

Критерии исключения

• History of hepatocellular carcinoma (HCC).
• History of any other primary or secondary malignant liver tumor.
• Diagnosis of malignancy or hematologic disorders within the past 5 years (without time limitation for hematologic malignancies).
• Patients currently undergoing hemodialysis.
• Pregnant or breastfeeding women.
• Individuals under legal protection (e.g., guardianship, curatorship) or unable to provide consent.
• Minors or individuals younger than 18 years.
• Individuals deprived of liberty by judicial or administrative order.
• Patients with psychiatric conditions receiving care under legal constraints (e.g., articles L.3212-1 and L.3213-1).
• Patients unable to comply with the study protocol requirements.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Франция · 1 центр

• Regional and University Hospital Center of Nancy — Vandœuvre-lès-Nancy

Публикации

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Идентификаторы

NCT: NCT06778317 · 2022-A01664-39

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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