Hepatic EncephalopathyEH-CASIMIRNCT05772585
Characterization of Metabolomic Fingerprints in Patients With Acute Liver Failure and Acute-on-chronic Liver Failure With Hepatic Encephalopathy
An observational study of Hepatic Encephalopathy and Acute Liver Failure, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Hepatic encephalopathy is a frequent complication of both acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) and could be responsible among other neurological complications of residual impairment after liver transplantation. Specific metabolomic studies have shed light into pathophysiology. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatic Encephalopathy, Acute Liver Failure, Acute on Chronic Liver Failure
- What is being tested?
- Blood collection
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Sep 2023to Apr 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
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
Study population: Patients hospitalised for acute or acute-on-chronic liver failure, with hepatic encephalopathy and receiving a liver transplant following medical progression
Who may be able to join
- age > 18 years
- patient presenting with:
- ALF (Synthetic liver failure (INR > 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within <26 weeks)
- or ACLF (≥ grade 1 from CANONIC criteria)
- with clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment
Who cannot join
- age < 18 years
- absence of HE
- LT without pre-existing HE
- patients who already undergone a LT
- other cause of neurological impairment
- Legally protected person
About this study
Official title: Characterization of Metabolomic Fingerprints in Patients With Acute Liver Failure and Acute-on-chronic Liver Failure With Hepatic Encephalopathy, and Influence of Liver Transplantation
Hepatic encephalopathy is a frequent complication of both acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) and could be responsible among other neurological complications of residual impairment after liver transplantation. Specific metabolomic studies have shed light into pathophysiology. Nevertheless, whether HE metabolomic fingerprints differ between HE in ALF and HE in ACLF and their evolution after liver transplantation (LT) is unknown.
The aim of our study is to analyse the metabolomic fingerprint in plasma of 2 different groups of patients before and after LT:
Read more
- hospitalized patients with ALF and HE
- hospitalized patients with ACLF and HE We will analyse metabolomic results to explore if there is any difference in metabolomic fingerprints between these 2 groups and if LT modify the metabolomic fingerprint in plasma in these 2 groups and in the same way.
We will collect blood samples in these 2 groups on the day of HE occurring and then on day 1, day 7 and day 30 (+/- 2 days) after LT. We aim to enroll 10 patients in ALF group and 20 patients in ACLF group.
Inclusion criteria are defined as age > 18 years, patient presenting with ALF (Synthetic liver failure (INR > 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within <26 weeks) or ACLF (≥ grade 1 from CANONIC criteria), and clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment. Exclusion criteria are defined as age < 18 years, absence of HE, LT without pre-existing HE, patients who already undergone a LT, legally protected person.
An EDTA blood sample will be collected, centrifuged and frozen on the day of enrolment, then on day 1, day 7 and day 30 (+/- 2 days) after LT. Metabolomic analyses will be performed by different techniques but especially with high resolution liquid phase mass spectrometry in collaboration with CEA. Statistical analyses will be both univariate (Mann-Whitney or Wilcoxon tests) and multivariate (with a classical and adapted method for metabolomic studies: Partial Least-Squares Discriminant Analysis (PLS-DA)).
We expect to identify different metabolomic fingerprints between HE in both ALF and ACLF patients as well as different kinetics for symptoms resolution after LT. The long-term objective is to target the specific metabolic pathways for each group in order to allow development of new targeted drugs against HE in these 2 different conditions.
Read the detailed description
Every patient admitted with hepatic encephalopathy and ALF or ACLF in Intensive Care Unit (ICU) or hepatology unit in both hospitals of Rennes University Hospital and La Pitié-Salpêtrière University Hospital will be screened by physicians for inclusion and exclusion criteria. If patients meet the criteria, their non-opposition of that of their next-of-kin (in case of disturbed neurological state) will be collected and an information paper will be given to them and their inclusion will be written in their medical file. On the same day (Day 0), a 6mL EDTA tube will be collected during a blood sample included in the standard patient care. Biological and demographic data collection will be done on day 0 too.
Then, patients will be followed-up during all the study duration and in case of LT, blood sample with 6mL EDTA tube will be collected on day 1, 7 and 30 after LT. Data collection will be performed at the time of each blood collection.
In case of the patient is not in hospital on the scheduled day, the blood collection will be performed on the very next outpatient consultation.
Every blood sample will be included as part of the blood samples for standard patient care and will under no circumstances be subject to a dedicated collection if the patient does not benefit from a test on the scheduled day.
If patient did not underwent LT during the follow-up, then only day 0 blood sample will be analyzed.
The blood samples will be centrifuged at 3000g for 10 min at 4°C, then the plasma will be collected and aliquoted in 4 Eppendorf with 400µL of plasma in each. All the aliquots will be stored at -80°C in the laboratories of the 2 centers.
After enrollment of the 30 expected patients, a secure transport network will be set up between the laboratories of the Rennes University Hospital and the Pitié-Salpêtrière University Hospital to the "Laboratoire d'Études du Métabolisme des Médicaments" of the CEA Saclay Center.
Processing and metabolomic analysis will be carried out in the CEA laboratory. These analyses will last approximately 2 weeks.
After having performed metabolites extraction in all the samples, high resolution liquid phase mass spectrometry will be done.
Finally, data analyses will be done with the CEA team and the manuscript will be written at the end of the study.
- Being tested
- Blood collection
- Keywords
- Hepatic Encephalopathy, Acute liver failure, Acute on chronic liver failure, Liver transplantation, Metabolomics
- Medical subject headings
- Hepatic Encephalopathy, Liver Failure, Acute, Acute-On-Chronic Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood collectionOther
Also called Metabolomics analyses, High resolution liquid phase mass spectrometry
Blood collection (1 to 4 times for each patient) in order to perform metabolomic analyses of the plasmatic fingerprints of patients with hepatic encephalopathy
| Study group | Role | What they receive |
|---|---|---|
| patients ALF and ACLF | patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with hepatic encephalopathy Receives: Other: Blood collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
comparison of metabolomic fingerprints of hepatic encephalopathy between ALF and ACLF
Partial Least-Squares Discriminant Analysis (PLS-DA).
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2023
- Study startSep 2023 (estimated)
- Primary completionApr 2024 (estimated)
- Study completionApr 2024 (estimated)
Why it stopped: competitor study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicolas WEISS, MD, PhD, Principal investigator, APHP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05772585
- Sponsor's protocol ID
- APHP221332
- Acronym
- EH-CASIMIR
- Status last verified
- Jul 2024
- First submitted
- 6 Mar 2023
- Last updated
- 1 Aug 2024
- 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 1 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Metabolomic Fingerprints in Patients With Acute Liver Failure and Acute-on-chronic Liver Failure With Hepatic Encephalopathy, and Influence of Liver Transplantation
- ClinicalTrials.gov ID
- NCT05772585
- Acronym / sponsor ID
- EH-CASIMIR / APHP221332
- Keywords
- Hepatic Encephalopathy, Acute liver failure, Acute on chronic liver failure, Liver transplantation, Metabolomics
- Study type
- Observational
- Recruitment status
- WithdrawnReason stopped: competitor study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Sep 2023 (estimated)
- Primary completion
- Apr 2024 (estimated)
- Study completion
- Apr 2024 (estimated)
- First posted
- 16 Mar 2023 (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.
Hepatic encephalopathy is a frequent complication of both acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) and could be responsible among other neurological complications of residual impairment after liver transplantation. Specific metabolomic studies have shed light into pathophysiology. Nevertheless, whether HE metabolomic fingerprints differ between HE in ALF and HE in ACLF and their evolution after liver transplantation (LT) is unknown.
The aim of our study is to analyse the metabolomic fingerprint in plasma of 2 different groups of patients before and after LT:
- hospitalized patients with ALF and HE
- hospitalized patients with ACLF and HE We will analyse metabolomic results to explore if there is any difference in metabolomic fingerprints between these 2 groups and if LT modify the metabolomic fingerprint in plasma in these 2 groups and in the same way.
We will collect blood samples in these 2 groups on the day of HE occurring and then on day 1, day 7 and day 30 (+/- 2 days) after LT. We aim to enroll 10 patients in ALF group and 20 patients in ACLF group.
Inclusion criteria are defined as age > 18 years, patient presenting with ALF (Synthetic liver failure (INR > 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within <26 weeks) or ACLF (≥ grade 1 from CANONIC criteria), and clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment. Exclusion criteria are defined as age < 18 years, absence of HE, LT without pre-existing HE, patients who already undergone a LT, legally protected person.
An EDTA blood sample will be collected, centrifuged and frozen on the day of enrolment, then on day 1, day 7 and day 30 (+/- 2 days) after LT. Metabolomic analyses will be performed by different techniques but especially with high resolution liquid phase mass spectrometry in collaboration with CEA. Statistical analyses will be both univariate (Mann-Whitney or Wilcoxon tests) and multivariate (with a classical and adapted method for metabolomic studies: Partial Least-Squares Discriminant Analysis (PLS-DA)).
We expect to identify different metabolomic fingerprints between HE in both ALF and ACLF patients as well as different kinetics for symptoms resolution after LT. The long-term objective is to target the specific metabolic pathways for each group in order to allow development of new targeted drugs against HE in these 2 different conditions.
Detailed description
Every patient admitted with hepatic encephalopathy and ALF or ACLF in Intensive Care Unit (ICU) or hepatology unit in both hospitals of Rennes University Hospital and La Pitié-Salpêtrière University Hospital will be screened by physicians for inclusion and exclusion criteria. If patients meet the criteria, their non-opposition of that of their next-of-kin (in case of disturbed neurological state) will be collected and an information paper will be given to them and their inclusion will be written in their medical file. On the same day (Day 0), a 6mL EDTA tube will be collected during a blood sample included in the standard patient care. Biological and demographic data collection will be done on day 0 too.
Then, patients will be followed-up during all the study duration and in case of LT, blood sample with 6mL EDTA tube will be collected on day 1, 7 and 30 after LT. Data collection will be performed at the time of each blood collection.
In case of the patient is not in hospital on the scheduled day, the blood collection will be performed on the very next outpatient consultation.
Every blood sample will be included as part of the blood samples for standard patient care and will under no circumstances be subject to a dedicated collection if the patient does not benefit from a test on the scheduled day.
If patient did not underwent LT during the follow-up, then only day 0 blood sample will be analyzed.
The blood samples will be centrifuged at 3000g for 10 min at 4°C, then the plasma will be collected and aliquoted in 4 Eppendorf with 400µL of plasma in each. All the aliquots will be stored at -80°C in the laboratories of the 2 centers.
After enrollment of the 30 expected patients, a secure transport network will be set up between the laboratories of the Rennes University Hospital and the Pitié-Salpêtrière University Hospital to the "Laboratoire d'Études du Métabolisme des Médicaments" of the CEA Saclay Center.
Processing and metabolomic analysis will be carried out in the CEA laboratory. These analyses will last approximately 2 weeks.
After having performed metabolites extraction in all the samples, high resolution liquid phase mass spectrometry will be done.
Finally, data analyses will be done with the CEA team and the manuscript will be written at the end of the study.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| patients ALF and ACLF | – | Other: Blood collectionpatients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) with hepatic encephalopathy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients hospitalised for acute or acute-on-chronic liver failure, with hepatic encephalopathy and receiving a liver transplant following medical progression
Key inclusion criteria (5 listed)
- age > 18 years
- patient presenting with:
- ALF (Synthetic liver failure (INR > 1.5) with hepatic encephalopathy (grade 1-4 of West-Haven classification), without pre-existing hepatopathy, HE beginning within <26 weeks)
- or ACLF (≥ grade 1 from CANONIC criteria)
- with clinical HE (grade 1-4 of West-Haven classification) on the day of enrolment
Key exclusion criteria (6 listed)
- age < 18 years
- absence of HE
- LT without pre-existing HE
- patients who already undergone a LT
- other cause of neurological impairment
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 collectionAlso: Metabolomics analyses, High resolution liquid phase mass spectrometryBlood collection (1 to 4 times for each patient) in order to perform metabolomic analyses of the plasmatic fingerprints of patients with hepatic encephalopathy | Other | patients ALF and ACLF |
Primary outcome
comparison of metabolomic fingerprints of hepatic encephalopathy between ALF and ACLF
Time frame: 6 months
Partial Least-Squares Discriminant Analysis (PLS-DA).
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Aug 2024.
- 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. This study is not recruiting at the moment.
Nicolas WEISS, MD, PhD principal investigator
APHP
Questions about this trial
What is this clinical trial studying?
An observational study of Hepatic Encephalopathy and Acute Liver Failure, run by Assistance Publique - Hôpitaux de Paris.
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: withdrawn, as of the sponsor's last update on 1 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
comparison of metabolomic fingerprints of hepatic encephalopathy between ALF and ACLF (time frame: 6 months). 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 1 Aug 2024.