MSEPT9 Biomarker for Predicting Hepatocellular Carcinoma Occurrence in Patients with Cirrhosis

NCT06778317 | Not Yet Recruiting FDA Device

• 1 other identifier: 2022-A01664-39
• Study Type: observational
• Target: 400
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Association Between mSEPT9 Test Switch and Hepatocellular Carcinoma (HCC) Development

  Evaluate the relationship between a 'switch' in the mSEPT9 test result-defined as a transition from triple-negative (no methylation detected across all triplicates) to at least one positive triplicate-and the occurrence of hepatocellular carcinoma (HCC), as diagnosed using international criteria established by the AASLD.

  Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.

Secondary Outcomes (3)

• Association Between mSEPT9 Test Switch and HCC Development by Cirrhosis Etiology

  Annually for up to 60 months or until the occurrence of HCC, whichever occurs first.

• Association Between mSEPT9 Test Results and HCC-Related Mortality

  Annually for up to 60 months or until HCC-specific death occurs.

• Establishment of a Biobank for Genomic and Epigenomic Analysis

  For each participant, samples will be collected at enrollment (baseline) and during follow-up visits every 6 months for up to 60 months.

Study Arms (1)

Patients With Cirrhosis Without Hepatocellular Carcinoma at Baseline

This cohort includes 400 patients with cirrhosis who do not have hepatocellular carcinoma (HCC) at the time of inclusion. Participants will undergo standard clinical, biological, and radiological evaluations every six months for a total follow-up duration of 60 months, in accordance with international guidelines for cirrhosis management. In addition to routine assessments, blood samples will be collected at each visit for the analysis of the circulating epigenetic biomarker mSEPT9. This biomarker will be tested to evaluate its utility in predicting the occurrence of HCC during the follow-up period. The results of the mSEPT9 test will not influence clinical management during the study.

Diagnostic Test: Circulating mSEPT9 Biomarker Testing

Interventions

Circulating mSEPT9 Biomarker Testing DIAGNOSTIC_TEST

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 carcinoma (HCC). The mSEPT9 test is conducted on plasma samples collected during routine blood draws at each of the 11 scheduled study visits. Samples are processed and analyzed in batches using specialized high-throughput equipment provided by Epigenomics/New Day Diagnostics. Results of the mSEPT9 test are not shared with clinicians during the study period to avoid influencing patient management, ensuring the test is purely investigational in this context.

Also known as: Plasma mSEPT9 Testing, Epigenetic Biomarker Analysis, mSEPT9 Methylation Test

Patients With Cirrhosis Without Hepatocellular Carcinoma at Baseline

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Central Hospital, Nancy, France: lead
• New Day Diagnostics: collaborator

Study Sites (1)

Regional and University Hospital Center of Nancy

Vandœuvre-lès-Nancy, 54511, France

Location

Related Publications (21)

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Biospecimen

Retention: SAMPLES WITH DNA

The biospecimens retained in this study include plasma samples and genetic material (DNA) collected from patients with cirrhosis during routine blood draws at each of the 11 scheduled visits (baseline and every 6 months for 60 months). For each visit, two 10 mL blood samples will be collected in EDTA tubes. Plasma will be extracted, aliquoted, and stored at -80°C for subsequent analysis of the mSEPT9 epigenetic biomarker.

MeSH Terms

Conditions

Carcinoma, Hepatocellular; Fibrosis

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Liver Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Liver Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mr. Franck Schreiner

  Regional and University Hospital Center of Nancy

  STUDY DIRECTOR

Central Study Contacts

Prof. Abderrahim OUSSALAH, MD, PhD

CONTACT

+33383153629; abderrahim.oussalah@univ-lorraine.fr

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 27, 2024
• First Posted: January 16, 2025
• Study Start: March 3, 2025
• Primary Completion (Estimated): March 4, 2030
• Study Completion (Estimated): March 3, 2031
• Last Updated: January 20, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Access Criteria: The individual participant data (IPD) and supporting information will be available starting 12 months after the publication of the study results. IPD related to outcomes outside the primary and secondary objectives of the study may be discussed and shared on a case-by-case basis, contingent on appropriate approvals and compliance with applicable regulations.

Locations

FR (1)