MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

NCT ID: NCT04116242

Last Updated: 2024-06-25

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

277 participants

Study Classification

OBSERVATIONAL

Study Start Date

2015-08-27

Study Completion Date

2024-06-10

Brief Summary

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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.

Detailed Description

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MER receptor tyrosine kinase (MERTK) signalling cascade becomes activated on monocytes/macrophages during disease progression of liver cirrhosis from Child Pugh A to B/C, corresponding to early stages of decompensation, and before the receptor expression is increased. Factors involved in activation of the MERTK signalling cascade might be microbial products such as bacterial deoxyribonucleic acid (DNA) and other toll-like receptor (TLR)-ligands, MERTK ligands and cytokines, as shown elevated in cirrhotic patients.

Given the observation that MERTK levels peak on the day of admission with organ failure and decrease in patients surviving the episode of acute-on-chronic liver failure (ACLF), MERTK Inhibition at a time during progression of cirrhosis but before manifestation of acute decompensation with no cirrhosis (AD) or ACLF might prevent infectious complications, decompensation and improve survival in patients with cirrhosis.

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

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

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

Intervention Type 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.

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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

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

Intervention Type 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.

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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

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

Intervention Type 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.

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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

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

Intervention Type 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

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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

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

Intervention Type 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.

healthy controls

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

blood sampling for research purpose

Intervention Type OTHER

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

clinical data collection

Intervention Type 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

Health-related Questionnaires

Intervention Type 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)

Interventions

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blood sampling for research purpose

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

Intervention Type OTHER

clinical data collection

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

Intervention Type OTHER

Health-related Questionnaires

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)

Intervention Type OTHER

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

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.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

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

Exclusion Criteria

* Evidence of disseminated malignancy
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Swiss National Science Foundation

OTHER

Sponsor Role collaborator

University Hospital, Basel, Switzerland

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christine Bernsmeier, PD Dr. Dr.

Role: PRINCIPAL_INVESTIGATOR

Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie

Locations

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University Hospital Basel, Hepatology Department and Laboratory

Basel, , Switzerland

Site Status

Cantonal Hospital St. Gallen

Sankt Gallen, , Switzerland

Site Status

King's College Hospital, Institute of Liver studies

London, , United Kingdom

Site Status

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

London, , United Kingdom

Site Status

Countries

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Switzerland United Kingdom

Other Identifiers

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EKSG 15/074; me19Bernsmeier2

Identifier Type: -

Identifier Source: org_study_id

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