MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

NCT04116242 | Completed

• 1 other identifier: EKSG 15/074; me19Bernsmeier2
• Study Type: observational
• Target: 277
• Locations: 2 countries
• Sites: 4

Brief Summary

This study is to investigate MER receptor tyrosine kinase (MERTK) signalling cascade on monocytes and tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, acute-on-chronic liver failure (ACLF)) and in comparison to patients with acute liver failure and to healthy controls.

Conditions

Liver Disease; Cirrhosis of the Liver; Acute-On-Chronic Liver Failure; Liver Failure

Keywords

immunoparesis; monocyte dysfunction; MER receptor tyrosine kinase (MERTK); innate immune dysfunction; circulating monocytes/macrophages; MERTK signalling

Outcome Measures

Primary Outcomes (2)

• Change in MERTK signalling cascade on monocytes

  Change in MERTK signalling cascade on monocytes in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, ACLF) and in comparison to patients with acute liver failure and to healthy controls

  days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months

• Change in MERTK signalling cascade on tissue macrophages

  Change in MERTK signalling cascade on tissue macrophages in respect to innate immune function of the cells in patients with cirrhosis at different stages of disease (Child A, B, C, acute decompensation, ACLF) and in comparison to patients with acute liver failure and to healthy controls

  days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months

Secondary Outcomes (1)

• Change in mechanism of MERTK activation in cell culture models using monocytes

  days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months

Study Arms (6)

cirrhosis of the liver, stadium Child A

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires; Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, stadium Child B

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires; Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, stadium Child C

sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires; Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

cirrhosis of the liver, acutely decompensated

sampling of biological material and health related data collection on days 1 (Baseline), 3, 7, and 14. If acutely decompensated patients re-compensate they will be followed 6-monthly for up to 36 months

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires; Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

acute liver failure

sampling of biological material and health related data collection on days 1 (Baseline), 3, 7, and 14. If acutely decompensated patients re-compensate they will be followed 6-monthly for up to 36 months

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires; Other: Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)

healthy controls

sampling of biological material and health related data collection on day 1 (Baseline)

Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires

Interventions

blood sampling for research purpose OTHER

blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place

acute liver failure; cirrhosis of the liver, acutely decompensated; cirrhosis of the liver, stadium Child A; cirrhosis of the liver, stadium Child B; cirrhosis of the liver, stadium Child C; healthy controls

clinical data collection OTHER

clinical data collection in order to document the stage of disease, the presence of infection and existing complications of cirrhosis (ascites, hepatic encephalopathy, renal dysfunction, pulmonary dysfunction) and concomitant disease. These data will be collected for clinical reasons as highly important in the context of patients with cirrhosis and possible decompensation or liver failure and will therefore not require additional time

acute liver failure; cirrhosis of the liver, acutely decompensated; cirrhosis of the liver, stadium Child A; cirrhosis of the liver, stadium Child B; cirrhosis of the liver, stadium Child C; healthy controls

Health-related Questionnaires OTHER

Health-related Questionnaires (Questionnaire\_CLD) regarding sleep characteristics (Pittsburgh sleep Quality index, PSQI), daytime sleepiness (Epworth sleepiness scale, ESS), anxiety and depression (Hospital Anxiety and Depression Scale, HADS) and quality of life (EQ-5D-5L)

acute liver failure; cirrhosis of the liver, acutely decompensated; cirrhosis of the liver, stadium Child A; cirrhosis of the liver, stadium Child B; cirrhosis of the liver, stadium Child C; healthy controls

Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) OTHER

Other biological material (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) will only be investigated if sampled for clinical reasons and if excessive material is available that is not needed for clinical purpose.

acute liver failure; cirrhosis of the liver, acutely decompensated; cirrhosis of the liver, stadium Child A; cirrhosis of the liver, stadium Child B; cirrhosis of the liver, stadium Child C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Prospective recruitment of patients with cirrhosis, acute decompensation, acute liver failure as pathological controls and healthy controls or controls with no liver disease at the Cantonal Hospital St. Gallen (KSSG), University Hospital Basel, St. Mary's Hospital, Imperial College London and King's College Hospital, London, UK.

You may qualify if:

• Patients with compensated or decompensated chronic liver disease
• Patients with acute- or acute-on-chronic chronic liver failure
• Controls with no liver disease

You may not qualify if:

• Evidence of disseminated malignancy

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Swiss National Science Foundation: collaborator

Study Sites (4)

University Hospital Basel, Hepatology Department and Laboratory

Basel, 4031, Switzerland

Location

Cantonal Hospital St. Gallen

Sankt Gallen, 9007, Switzerland

Location

King's College Hospital, Institute of Liver studies

London, SE5 9RS, United Kingdom

Location

St. Mary's Hospital, Imperial College London, Section of Hepatology

London, W2 1PG, United Kingdom

Location

Biospecimen

Retention: SAMPLES WITH DNA

Biological material will be stored in -80°C and -140°C freezers at the sites of recruitment. If biological material (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies) are sampled routinely for clinical reasons and exceeding material allows additional scientific investigations, a small amount of the material will be used. The samples will be destroyed 10 years after publication of the study

MeSH Terms

Conditions

Liver Diseases; Fibrosis; Acute-On-Chronic Liver Failure; Liver Failure

Interventions

Blood Specimen Collection; Hepatectomy; Urination

Condition Hierarchy (Ancestors)

Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure, Acute; Hepatic Insufficiency

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques; Digestive System Surgical Procedures; Urinary Tract Physiological Phenomena; Reproductive and Urinary Physiological Phenomena

Study Officials

• Christine Bernsmeier, PD Dr. Dr.

  Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 3, 2019
• First Posted: October 4, 2019
• Study Start: August 27, 2015
• Primary Completion: June 10, 2024
• Study Completion: June 10, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Locations

CH (2); GB (2)