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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 : November 18, 2021
Sponsor:
Collaborator:
Swiss National Science Foundation
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

Tracking Information
First Submitted Date October 3, 2019
First Posted Date October 4, 2019
Last Update Posted Date November 18, 2021
Actual Study Start Date August 27, 2015
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: October 3, 2019)
  • 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
  • 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
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures
 (submitted: October 3, 2019)
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
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
Official Title MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
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.
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.

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:

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

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.
Condition
  • Liver Disease
  • Cirrhosis of the Liver
  • Acute-On-Chronic Liver Failure
  • Liver Failure
Intervention
  • 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.
Study Groups/Cohorts
  • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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
    Interventions:
    • 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)
    Interventions:
    • Other: blood sampling for research purpose
    • Other: clinical data collection
    • Other: Health-related Questionnaires
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Recruiting
Estimated Enrollment
 (submitted: October 3, 2019)
240
Original Estimated Enrollment Same as current
Estimated Study Completion Date December 2022
Estimated Primary Completion Date August 2022   (Final data collection date for primary outcome measure)
Eligibility 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
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers Yes
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
Listed Location Countries Switzerland,   United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number NCT04116242
Other Study ID Numbers EKSG 15/074; me19Bernsmeier2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement Not Provided
Responsible Party University Hospital, Basel, Switzerland
Study Sponsor University Hospital, Basel, Switzerland
Collaborators Swiss National Science Foundation
Investigators
Principal Investigator: Christine Bernsmeier, PD Dr. Dr. Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie
PRS Account University Hospital, Basel, Switzerland
Verification Date November 2021