Chronic Liver DiseaseMALAHBARNCT06318949
Albumin Modifications as Early Biomarkers of Chronic Liver Diseases
A study testing blood sampling in people with Chronic Liver Disease, run by University Hospital, Limoges at 7 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Liver Disease
- What is being tested?
- blood sampling
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 756 participants
- Where
- 7 sitesin 2 countries
- Study dates
- 9 Dec 2024to 1 Dec 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- At least 18 years old
- With a compensated fibrosis defined by an hepatic elasticity ≥10 kPa measured by FibroScan®
- Having had blood test at the hospital as part of a consultation or an hospitalisation at the inclusion including usual parameters for the liver disease follow-up
- Affiliated with or beneficiaries of a social security system
- Not opposed to participate to the study after being informed
Who cannot join
- Patients suffering from decompensated cirrhosis or with an history of decompensated cirrhosis
- Patients who received an albumin infusion in the month before the inclusion visit
- 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
Trial locations and contacts
7 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
7 sites in 2 countries
France6 sites, 6 recruiting
- Recruiting
Angers Univeristy Hospital
Angers, 49100
Jerome BOURSIER, MD, JeBoursier@chu-angers.fr
Jerome BOURSIER, MD
- Recruiting
Limoges University Hospital
Limoges, 87042
Souleiman EL BALKHI, MD, Souleiman.ElBalkhi@chu-limoges.fr
Paul CARRIER, MD, Paul.Carrier@chu-limoges.fr
- Recruiting
Poitiers University Hospital
Poitiers, 86000
Valentin ROLLE, MD, v.rolle@chu-poitiers.fr
Valentin ROLLE, MD
- Recruiting
Rennes University Hospital
Rennes, 35000
Florent ARTRU, MD, florent.artru@chu-rennes.fr
Florent ARTRU, MD
- Recruiting
Toulouse University Hospital
Toulouse, 31400
Christophe BUREAU, MD, bureau.c@chu-toulouse.fr
Christophe BUREAU, MD
- Not yet recruiting
Tours University Hospital
Tours, 37170
Laure ELKRIEF, MD, l.elkrief@chu-tours.fr
Laure ELKRIEF, MD
Guadeloupe1 site, 1 recruiting
- Not yet recruiting
Pointe à Pitre University Hospital
Pointe-à-Pitre, 97159
Moana GELU-SIMEON, moana.simeon@chu-guadeloupe.fr
Moana GELU-SIMEON, MD
About this study
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.
Read the detailed description
More than 800 million people suffer from chronic liver disease (CLD) with approximately 2 million deaths per year. The progression of CLD, could be asymptomatic until the appearance of fibrosis, cirrhosis and sometimes hepatocellular carcinoma. The prevention and early diagnosis of liver disease is therefore a major public health issue.
Due to their lack of sensitivity and specificity, direct serum markers are now combined in " panel tests ", sometimes gathered and used in algorithms (FibroMeter, FibroTest, FIBROSpect, Hepascore…) to help diagnose fibrosis or cirrhosis and to assess the stage of liver damage. Other biomarkers, in particular molecules involved in the fibrosis process, (protein-based biomarkers, microRNA or collagen-based biomarkers) have been the subject of numerous studies, but have not yet led to clinically exploitable biomarkers for the medium- or long-term monitoring of CLD. Non-invasive, sensitive and specific biomarkers for the early detection of liver dysfunction leading to advanced liver disease are therefore still awaited.
It has been shown that chemical and structural modifications of human serum albumin (HAS) leading to different isoforms could be used as biomarkers for advanced liver disease. Our work supports the hypothesis that the main changes in HSA occur in the early stages of cellular liver damage and could be predictive of future liver disease. These modifications can be revealed by the profile of isoforms in the patient's serum, or even more efficiently by the binding capacities of HAS for different ligands with specific binding sites. On this basis, a patent application has been filed for the SEB (Serum enhanced binding) test.
The study plans to recruit 756 patients in 6 university hospital centers (CHU of Limoges, Angers, Poitiers, Tours, Rennes, and Pointe à Pitre). The recruitment period is of 1.5 year.
Each patient will be followed during 3 years maximumThe study requires no supplementary visit as compared to the standard care. Study visits will take place during usual visits of the standard care as follows:.
- Inclusion visit : study information by the investigator and if the patient is not opposed to participate to the study, either blood sampling (a supplementary tube can be add to a routine blood sampling realised for standard cares) or re-use of a residual blood sample after routine tests have been done, and data collection from the medical file.
- Follow-up visits: visits at 1, 2 and 3 years depending to the diagnostic of the investigator. During these visits: collection of a blood sampling the same conditions described for the inclusion visit and data collection from the medical file.
The samples will be sent to the central laboratory in the CHU of Limoges (Pharmacology, Toxicology and Pharmacovigilance) where HSA isoforms will be analysed by LC-QTOF and SEB tests realised.
The main goal is to validate HAS modifications as biomarker able to predict the evolution of liver damage and thus prevent worsening of the liver disease and finally improve the quality of care.
- Conditions
- Chronic Liver Disease
- Being tested
- blood sampling
- Keywords
- predictive early biomarkers, albumine modifications, liver damage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood samplingProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| experimental arm | Experimental | Not described Receives: Procedure: blood sampling |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
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 the occurrence of one or several events of the following:
- Liver-related events
- Worsening of the disease stage evaluated by the Child Pugh score or of 2 points of the MELD score in case of cirrhosis.
Measured: 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.
Positive predictive value (VPP) of post-translational HSA modifications related to the worsening of the liver damage at 1 and 2 years. This will be determined by the occurrence of one or several events of the following
Measured: 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).
Positive predictive value of the SEB test related to the worsening of the liver damage at 3 years, and at 1 and 2 years provided data are available in medical files.
Measured: Year 3
diagnostic performances of the SEB test and of the different isoforms of HSA at each stage of the liver disease.
Sensibility and specificity of the SEB test and of the different isoforms of HAS, at each stage of the . liver disease (Child Pugh A5, A6, B7, B8, B9, et > C10).
Measured: 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.
Ability to discriminate patients depending on the cause of the initial liver damage, taking into account the whole patterns of isoforms (including minor isoforms), with calculation of sensibility and specificity.
Measured: Years 3
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2024
- Study start9 Dec 2024
- Primary completion1 Jun 2029 (estimated)
- Study completion1 Dec 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, LimogesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Prospective multicentre study of biomarker validation
- Masking
- None (open label)
- Enrolment
- 756 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Limoges
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06318949
- Sponsor's protocol ID
- 87RI22_0007 (MALAHBAR)
- Acronym
- MALAHBAR
- Status last verified
- Feb 2025
- First submitted
- 12 Mar 2024
- Last updated
- 12 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Albumin Modifications as Early Biomarkers of Chronic Liver Diseases
- ClinicalTrials.gov ID
- NCT06318949
- Acronym / sponsor ID
- MALAHBAR / 87RI22_0007 (MALAHBAR)
- Conditions
- Chronic Liver Disease
- Keywords
- predictive early biomarkers, albumine modifications, liver damage
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 756 participants (estimated)
- Lead sponsor
- University Hospital, LimogesUniversity, hospital or other
- Study start
- 9 Dec 2024 (actual)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 1 Dec 2029 (estimated)
- First posted
- 19 Mar 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
More than 800 million people suffer from chronic liver disease (CLD) with approximately 2 million deaths per year. The progression of CLD, could be asymptomatic until the appearance of fibrosis, cirrhosis and sometimes hepatocellular carcinoma. The prevention and early diagnosis of liver disease is therefore a major public health issue.
Due to their lack of sensitivity and specificity, direct serum markers are now combined in " panel tests ", sometimes gathered and used in algorithms (FibroMeter, FibroTest, FIBROSpect, Hepascore…) to help diagnose fibrosis or cirrhosis and to assess the stage of liver damage. Other biomarkers, in particular molecules involved in the fibrosis process, (protein-based biomarkers, microRNA or collagen-based biomarkers) have been the subject of numerous studies, but have not yet led to clinically exploitable biomarkers for the medium- or long-term monitoring of CLD. Non-invasive, sensitive and specific biomarkers for the early detection of liver dysfunction leading to advanced liver disease are therefore still awaited.
It has been shown that chemical and structural modifications of human serum albumin (HAS) leading to different isoforms could be used as biomarkers for advanced liver disease. Our work supports the hypothesis that the main changes in HSA occur in the early stages of cellular liver damage and could be predictive of future liver disease. These modifications can be revealed by the profile of isoforms in the patient's serum, or even more efficiently by the binding capacities of HAS for different ligands with specific binding sites. On this basis, a patent application has been filed for the SEB (Serum enhanced binding) test.
The study plans to recruit 756 patients in 6 university hospital centers (CHU of Limoges, Angers, Poitiers, Tours, Rennes, and Pointe à Pitre). The recruitment period is of 1.5 year.
Each patient will be followed during 3 years maximumThe study requires no supplementary visit as compared to the standard care. Study visits will take place during usual visits of the standard care as follows:.
- Inclusion visit : study information by the investigator and if the patient is not opposed to participate to the study, either blood sampling (a supplementary tube can be add to a routine blood sampling realised for standard cares) or re-use of a residual blood sample after routine tests have been done, and data collection from the medical file.
- Follow-up visits: visits at 1, 2 and 3 years depending to the diagnostic of the investigator. During these visits: collection of a blood sampling the same conditions described for the inclusion visit and data collection from the medical file.
The samples will be sent to the central laboratory in the CHU of Limoges (Pharmacology, Toxicology and Pharmacovigilance) where HSA isoforms will be analysed by LC-QTOF and SEB tests realised.
The main goal is to validate HAS modifications as biomarker able to predict the evolution of liver damage and thus prevent worsening of the liver disease and finally improve the quality of care.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Prospective multicentre study of biomarker validation
| Arm | Type | Receives |
|---|---|---|
| experimental arm | Experimental | Procedure: blood sampling |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- At least 18 years old
- With a compensated fibrosis defined by an hepatic elasticity ≥10 kPa measured by FibroScan®
- Having had blood test at the hospital as part of a consultation or an hospitalisation at the inclusion including usual parameters for the liver disease follow-up
- Affiliated with or beneficiaries of a social security system
- Not opposed to participate to the study after being informed
Key exclusion criteria (6 listed)
- Patients suffering from decompensated cirrhosis or with an history of decompensated cirrhosis
- Patients who received an albumin infusion in the month before the inclusion visit
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood samplingIf 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. | Procedure or surgery | experimental arm |
Primary outcome
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.
Time frame: Years 3
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.
5 secondary outcomes
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.
Time frame: 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.
Time frame: 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).
Time frame: Year 3
diagnostic performances of the SEB test and of the different isoforms of HSA at each stage of the liver disease.
Time frame: 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.
Time frame: Years 3
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
7 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood sampling in people with Chronic Liver Disease, run by University Hospital, Limoges at 7 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in France, Guadeloupe. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Souleiman EL BALKHI, MD (0555058035, Souleiman.ElBalkhi@chu-limoges.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: Years 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2025.