Ignite Creation Date:
2024-05-06 @ 6:46 PM
Last Modification Date:
2024-10-26 @ 2:54 PM
Study NCT ID:
NCT05772585
Status:
WITHDRAWN
Last Update Posted:
2023-03-16
First Post:
2023-03-06
Brief Title:
Characterization of Metabolomic Fingerprints in Patients With Acute Liver Failure and Acute-on-chronic Liver Failure With Hepatic Encephalopathy
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
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
Status:
WITHDRAWN
Status Verified Date:
2024-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
competitor study
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
EH-CASIMIR
Brief 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 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 15 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
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 15 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 4C then the plasma will be collected and aliquoted in 4 Eppendorf with 400µL of plasma in each All the aliquots will be stored at -80C 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 dÉtudes 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
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 4C then the plasma will be collected and aliquoted in 4 Eppendorf with 400µL of plasma in each All the aliquots will be stored at -80C 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 dÉtudes 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None