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MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

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ClinicalTrials.gov Identifier: NCT04116242
Recruitment Status : Recruiting
First Posted : October 4, 2019
Last Update Posted : October 4, 2019
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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.

Condition or disease Intervention/treatment
Liver Disease Cirrhosis of the Liver Acute-On-Chronic Liver Failure Liver Failure 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)

Detailed Description:

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.

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Study Type : Observational
Estimated Enrollment : 240 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
Actual Study Start Date : August 27, 2015
Estimated Primary Completion Date : August 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Liver Diseases

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

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

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)

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.

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

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

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)

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.

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

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

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)

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.

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

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

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)

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.

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

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

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)

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.

healthy controls
sampling of biological material and health related data collection on day 1 (Baseline)
Other: blood sampling for research purpose
blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place

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

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)




Primary Outcome Measures :
  1. Change in MERTK signalling cascade on monocytes [ Time Frame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months ]
    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

  2. Change in MERTK signalling cascade on tissue macrophages [ Time Frame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months ]
    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


Secondary Outcome Measures :
  1. Change in mechanism of MERTK activation in cell culture models using monocytes [ Time Frame: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months ]
    Change in mechanism of MERTK activation in cell culture models using healthy and diseased monocytes in vitro and ex vivo


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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04116242


Contacts
Layout table for location contacts
Contact: Christine Bernsmeier, PD Dr. Dr. +41 61 77 77575 C.Bernsmeier@unibas.ch
Contact: Markus Heim, Prof. Dr. MD +41 61 77 77490 markus.heim@usb.ch

Locations
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Switzerland
University Hospital Basel, Hepatology Department and Laboratory Recruiting
Basel, Switzerland, 4031
Contact: Markus Heim, Prof. Dr. MD    +41 61 265 55 19    markus.heim@usb.ch   
Cantonal Hospital St. Gallen Recruiting
St. Gallen, Switzerland, 9007
Contact: Christine Bernsmeier, PD Dr. Dr.    +41 71 494 11 11    Christine.Bernsmeier@kssg.ch   
United Kingdom
King's College Hospital, Institute of Liver studies Recruiting
London, United Kingdom, SE5 9RS
Contact: Julia A Wendon, Prof.    +44 20 3299 3367    Julia.wendon@kcl.ac.uk   
St. Mary's Hospital, Imperial College London, Section of Hepatology Recruiting
London, United Kingdom, W2 1PG
Contact: Charalambos G Antoniades, Dr. med    +44 20 331 21903    c.antoniades@imperial.ac.uk   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Swiss National Science Foundation
Investigators
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Principal Investigator: Christine Bernsmeier, PD Dr. Dr. Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie

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Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT04116242    
Other Study ID Numbers: EKSG 15/074; me19Bernsmeier2
First Posted: October 4, 2019    Key Record Dates
Last Update Posted: October 4, 2019
Last Verified: October 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Basel, Switzerland:
immunoparesis
monocyte dysfunction
MER receptor tyrosine kinase (MERTK)
innate immune dysfunction
circulating monocytes/macrophages
MERTK signalling
Additional relevant MeSH terms:
Layout table for MeSH terms
Liver Diseases
Liver Failure
Hepatic Insufficiency
End Stage Liver Disease
Acute-On-Chronic Liver Failure
Liver Cirrhosis
Digestive System Diseases
Liver Failure, Acute
Liver Extracts
Hematinics