Metobolomics in the Characterisation of HE

NCT06245473 | Completed

• 1 other identifier: APHP220279
• Study Type: observational
• Target: 1
• Locations: 1 country
• Sites: 2

Brief Summary

Hepatic encephalopathy is (HE) defined by the neurological and/or neuropsychological symptoms caused by an acute or chronic liver disease and/or a portosystemic shunt. Its pathophysiology is still debated, although the synergic role of hyperammonemia and inflammation is now admitted for years. Several additional mechanisms have been suspected, one of them being an altered permeability of the brain blood barrier (BBB). Nevertheless, many aspects remain poorly understood. The rise of "-omics" techniques, and especially metabolomics, allowed to identify more precisely the different metabolic pathways that are involved in the pathophysiology of HE. Using a high flow chemistry technique and multivariate data analysis, metabolomics is an accurate way to understand the pathophysiology and pathogenesis of multifactorial diseases such as HE. Several studies have been published in cirrhosis. It has been suggested that serum metabolites at admission, as well as thyroxine, can predict advanced HE in patients without brain failure. In a cohort including more than 600 patients, a higher microbially-derived metabolites, together with a lower thyroxine level, were associated with further development of brain failure. In another study from the same team, serum and urinary metabolites were significantly different in hospitalised patients who had developed poor outcome or not. Another study conducted in the CANONIC cohort as also found changes in metabolites of patients with cirrhosis and acute-on-chronic liver failure (ACLF), revealing mitochondrial dysfunction in peripheral organs that may contribute to organ failures. Last, our team previously analysed plasma and cerebrospinal fluid (CSF) samples of patients with cirrhosis and HE hospitalised in intensive care unit (ICU), showing alteration in ammonia and amino-acids metabolism, and also in energy metabolism. However, in the latest study, ALCF grading was not available. As many of these patients were in a severe condition, one could hypothesize that the metabolomic changes observed in these patients may have been confounded by an ACLF profile. Therefore, the objective of this study is to characterize the metabolomic fingerprints of HE in patients with cirrhosis, using 4 different groups of patients: patients with or without HE, with or without ALCF.

Conditions

Hepatic Encephalopathy; Cirrhosis

Keywords

Hepatic encephalopathy; Cirrhosis; Metabolomics

Outcome Measures

Primary Outcomes (1)

• Metabolomic analysis by mass spectrometry from a 6mL blood sample of cirrhotic patients.

  At the inclusion visit

Interventions

blood sample DIAGNOSTIC_TEST

During the blood test planned as part of the care an additional blood tube with a volume of 6mL will be takeń in an EDTA tube.

Eligibility Criteria

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

Study Population

Patients over 18 years of age with cirrhosis according to the presence of ACLF or hepatic encephalopathy or not.

You may qualify if:

• Patient aged ≥ 18 years
• Patient with cirrhosis of any etiology
• Informed patient who does not object to participating in the study
• Patient affiliated to a social security scheme or entitled beneficiary

You may not qualify if:

• Pregnant or breast-feeding women
• Protected populations: under guardianship or trusteeship
• Previous liver transplant
• Patient on AME

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (2)

Service d'hépato-gastroentérologie Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

Sorbonne University, Pitié salpêtrière hospital

Paris, Île-de-France Region, 75013, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

6-mL tube for metabolomic analysis during a blood test scheduled as part of treatment

MeSH Terms

Conditions

Hepatic Encephalopathy; Fibrosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Marika Rudler, MD, PhD

  Sorbonne University, Pitié salpêtrière hospital

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 7, 2024
• Study Start: April 23, 2024
• Primary Completion: April 23, 2024
• Study Completion: April 23, 2024
• Last Updated: April 3, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 3 years following article publication. Requests out of these time frame can also be submitted to the sponsor
• Access Criteria: Researchers who provide a methodologically sound proposal.

Locations

FR (2)