Albumin Modifications as Early Biomarkers of Chronic Liver Diseases

NCT06318949 | Recruiting

• 1 other identifier: 87RI22_0007 (MALAHBAR)
• Study Type: interventional
• Target: 756
• Locations: 2 countries
• Sites: 7

Brief Summary

Chronic liver diseases, affecting over 800 million people worldwide, lead to approximately 2 million annual deaths. The need for early, sensitive diagnostic strategies to prevent disease progression and reduce mortality is still unmet. The traditional serum markers lack sensitivity and specificity, leading to the integration of these biomarkers into panel tests with algorithms or imaging measures. Despite their widespread use, these tests have limitations at an individual level, including an inability to predict disease progression or response to treatment. To address these shortcomings, our project proposes utilizing albumin post-translational modifications (PTM) as a predictive biomarker for liver disease progression. The hypothesis is that albumin modifications occur in the early stages of hepatocellular damage and are indicative of future liver diseases. These modifications can be detected through serum albumin isoform determination, albumin isoforms profiles or the albumin's ligand-binding capacities. Innovatively, the study will use the Serum Enhanced Binding (SEB) test, which identifies reduced ligand-binding capacities, and discusses a second patent for determining a typical isoform profile based on the hepatic injury type. Our preliminary results from animal models and a proof-of-concept studies with patients support this hypotheses. Our previous studies demonstrated also significant differences in albumin isoform profiles in response to different types of hepatic injury and high sensitivity and specificity in the SEB test among cirrhotic patients. The primary objective of the MALAHBAR project is to evaluate the capacity of albumin PTM to predict liver disease progression over three years in chronic liver disease patients. Secondary objectives include assessing the predictive ability of different albumin isoforms and the SEB test for liver disease progression, evaluating diagnostic performances and confirming characteristic albumin isoform profiles related to specific hepatic injuries. The study could represent a significant advancement in liver disease diagnostics and management, offering new insights into the role of albumin in liver pathology.

Conditions

Chronic Liver Disease

Keywords

predictive early biomarkers; albumine modifications; liver damage

Outcome Measures

Primary Outcomes (1)

• Ability of HSA PTM to predict the evolution of liver damage at 3 year in patients with an advanced chronic liver disease (ACLD) as recently defined in the BAVENO VII recommendations based on FibroScan.

  The primary outcome is the positive predictive value (VPP) of post-translational HSA modifications related to the worsening of the liver damage at 3 years . This will be determined by an augmentation of more than 20% as compared to the initial state, documented by FibroScan® or a liver related event as defined in BAVENO VII.

  Years 3

Secondary Outcomes (5)

• ability of post-translational HSA modifications to predict the evolution of liver damage at 3 years based on liver-related events or on the worsening of the disease stage evaluated by the de Child Pugh or MELD score.

  Year 3

• ability of the different isoforms of HSA to predict the evolution of liver damage at 1 and 2 years provided that data are available in the medical file.

  year 2

• ability of SEB test to predict the evolution of liver damage at 3 years (and at 1 and 2 years provided data are available in the medical file).

  Year 3

• diagnostic performances of the SEB test and of the different isoforms of HSA at each stage of the liver disease.

  year 3

• confirm that the isoforms of HAS present in the characteristic patterns (type of isoform and intensity) of the nature of the liver damage.

  Years 3

Study Arms (1)

experimental arm

EXPERIMENTAL

Procedure: blood sampling

Interventions

blood sampling PROCEDURE

If the patient does not object to participating in the study, a blood sample is taken at each visit (an additional tube may be added to a routine blood sample taken for standard care), or a residual blood sample is reused after routine tests have been performed, and data is collected from the medical record.

experimental arm

Eligibility Criteria

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

You may qualify if:

• At least 18 years old
• With a compensated fibrosis defined by an hepatic elasticity ≥10 kPa measured by FibroScan®
• Affiliated with or beneficiaries of a social security system
• Not opposed to participate to the study after being informed

You may not qualify if:

• Patients suffering from decompensated cirrhosis or with an history of decompensated cirrhosis
• Patients suffering from stage 4 or 5 renal failure (GFR \< 29 ml/min/1,73m²)
• Patients suffering from cancer
• Pregnant or breastfeeding women or women of childbearing age without effective contraception (based on declaration)
• Patients suffering from impairment of mental faculties or a psychiatric disorder which could interfere with the understanding of the study

Sponsors & Collaborators

• University Hospital, Limoges: lead

Study Sites (7)

Angers Univeristy Hospital

Angers, 49100, France

RECRUITING

Limoges University Hospital

Limoges, 87042, France

RECRUITING

Poitiers University Hospital

Poitiers, 86000, France

RECRUITING

Rennes University Hospital

Rennes, 35000, France

RECRUITING

Toulouse University Hospital

Toulouse, 31400, France

RECRUITING

Tours University Hospital

Tours, 37170, France

NOT YET RECRUITING

Pointe à Pitre University Hospital

Pointe-à-Pitre, 97159, Guadeloupe

NOT YET RECRUITING

MeSH Terms

Interventions

Blood Specimen Collection

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Central Study Contacts

Souleiman EL BALKHI, MD

CONTACT

0555058035; Souleiman.ElBalkhi@chu-limoges.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective multicentre study of biomarker validation

Study Record Dates

• First Submitted: March 12, 2024
• First Posted: March 19, 2024
• Study Start: December 9, 2024
• Primary Completion (Estimated): June 1, 2029
• Study Completion (Estimated): December 1, 2029
• Last Updated: February 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

GU (1); FR (6)