Clinical trial NCT06778317: MSEPT9 Biomarker for Predicting Hepatocellular Carcinoma Occurrence in Patients with Cirrhosis
Official title: Evaluation of the Circulating Epigenetic Biomarker MSEPT9 for Predicting the Occurrence of Hepatocellular Carcinoma in Patients with Cirrhosis: a Prospective Multicenter Trial (SEPT9_SuRV)
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Hepatocellular Carcinoma (HCC)
Cirrhosis
Risk Prediction for Liver Cancer
Epigenomics
Keywords: Hepatocellular Carcinoma
Cirrhosis
mSEPT9 Biomarker
Epigenetics
Risk Prediction
Liver Cancer Surveillance
Prospective Cohort Study
Non-Invasive Biomarkers
Personalized Medicine
Epigenomics
Risk Stratification
Lead sponsor: Central Hospital, Nancy, France
Sponsor class: OTHER
Collaborators: name: New Day Diagnostics
First posted: 2025-01-16
Enrollment: 400
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study population consists of 400 adult patients with confirmed cirrhosis who are actively followed in specialized hepatology centers across multiple institutions. Participants must not have hepatocellular carcinoma (HCC) at the time of enrollment and must meet specific inclusion criteria, including established cirrhosis etiology and eligibility for routine clinical follow-up. Patients with conditions that may interfere with the study objectives, such as a history of malignancy or ongoing hemodialysis, are excluded. This cohort represents a diverse range of cirrhosis etiologies, including viral hepatitis, alcohol-related liver disease, and nonalcoholic steatohepatitis (NASH), to ensure the generalizability of findings.

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Association Between mSEPT9 Test Switch and Hepatocellular Carcinoma (HCC) Development
timeFrame: Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.
Secondary outcomes:
measure: Association Between mSEPT9 Test Switch and HCC Development by Cirrhosis Etiology
timeFrame: Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.
measure: Association Between mSEPT9 Test Results and HCC-Related Mortality
timeFrame: Annually for up to 60 months or until HCC-specific death occurs.
measure: Establishment of a Biobank for Genomic and Epigenomic Analysis
timeFrame: For each participant, samples will be collected at enrollment (baseline) and during follow-up visits every 6 months for up to 60 months.
Other outcomes:
Locations:
city: Vandoeuvre-lès-Nancy
country: France
facility: Regional and University Hospital Center of Nancy
Study officials:
affiliation: Regional and University Hospital Center of Nancy
name: Mr. Franck Schreiner
role: STUDY_DIRECTOR
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