MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

Liver Disease Clinical Trial

Official title:

MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04116242
• Other study ID #: EKSG 15/074; me19Bernsmeier2
• Status: Recruiting
• Start date: August 27, 2015
• Est. completion date: December 2022

Study information

• Verified date: November 2021
• Source: University Hospital, Basel, Switzerland
• Contact: Christine Bernsmeier, PD Dr. Dr.
• Phone: +41 61 77 77575
• Email: C.Bernsmeier[@]unibas.ch
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: December 2022
• Est. primary completion date: August 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• Cirrhosis of the Liver
• End Stage Liver Disease
• Hepatic Insufficiency
• Liver Cirrhosis
• Liver Disease
• Liver Diseases
• 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
• 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
• 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)
• 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.

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Hepatology Department and Laboratory	Basel
Switzerland	Cantonal Hospital St. Gallen	St. Gallen
United Kingdom	King's College Hospital, Institute of Liver studies	London
United Kingdom	St. Mary's Hospital, Imperial College London, Section of Hepatology	London

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland	Swiss National Science Foundation

Countries where clinical trial is conducted

Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change in mechanism of MERTK activation in cell culture models using monocytes	Change in mechanism of MERTK activation in cell culture models using healthy and diseased monocytes in vitro and ex vivo	days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months