Liver DiseaseNCT04116242
MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
An observational study of Liver Disease and Cirrhosis of the Liver, run by University Hospital, Basel, Switzerland at 4 sites in 2 countries.
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… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Liver Disease, Cirrhosis of the Liver, Acute-On-Chronic Liver Failure
- What is being tested?
- blood sampling for research purpose, clinical data collection and Health-related Questionnaires
- Type of treatment
- Injection or infusion
- How many people
- 277 participants
- Where
- 4 sitesin 2 countries
- Study dates
- 27 Aug 2015to 10 Jun 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- Patients with compensated or decompensated chronic liver disease
- Patients with acute- or acute-on-chronic chronic liver failure
- Controls with no liver disease
Who cannot join
- Evidence of disseminated malignancy
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
Switzerland2 sites
University Hospital Basel, Hepatology Department and Laboratory
Basel, 4031
Cantonal Hospital St. Gallen
Sankt Gallen, 9007
United Kingdom2 sites
King's College Hospital, Institute of Liver studies
London, SE5 9RS
St. Mary's Hospital, Imperial College London, Section of Hepatology
London, W2 1PG
About this study
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.
Read the 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.
- Being tested
- blood sampling for research purpose, clinical data collection, Health-related Questionnaires, Sampling other biological materials (e.g. liver biopsies, liver resections, ascites, urine, gut biopsies)
- Keywords
- immunoparesis, monocyte dysfunction, MER receptor tyrosine kinase (MERTK), innate immune dysfunction, circulating monocytes/macrophages, MERTK signalling
- Medical subject headings
- Liver Diseases, Fibrosis, Acute-On-Chronic Liver Failure, Liver Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood sampling for research purposeOther
blood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place
clinical data collectionOther
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 QuestionnairesOther
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
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 group | Role | What they receive |
|---|---|---|
| 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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 Receives: 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) Receives: Other: blood sampling for research purpose; Other: clinical data collection; Other: Health-related Questionnaires |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: 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
Change in mechanism of MERTK activation in cell culture models using healthy and diseased monocytes in vitro and ex vivo
Measured: days 1 (Baseline), 3, 7, and 14; then followed 6-monthly for up to 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Oct 2019
- Study start27 Aug 2015
- Primary completion10 Jun 2024
- Study completion10 Jun 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver DiseaseStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 277 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss National Science Foundation
- Responsible party
- Sponsor
- Investigators
- Christine Bernsmeier, PD Dr. Dr., Principal investigator, Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04116242
- Sponsor's protocol ID
- EKSG 15/074; me19Bernsmeier2
- Status last verified
- Jun 2024
- First submitted
- 3 Oct 2019
- Last updated
- 25 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MERTK Signalling in Monocytes/Macrophages in Patients With Liver Disease
- ClinicalTrials.gov ID
- NCT04116242
- Acronym / sponsor ID
- EKSG 15/074; me19Bernsmeier2
- Keywords
- immunoparesis, monocyte dysfunction, MER receptor tyrosine kinase (MERTK), innate immune dysfunction, circulating monocytes/macrophages, MERTK signalling
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 277 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Swiss National Science Foundation
- Study start
- 27 Aug 2015 (actual)
- Primary completion
- 10 Jun 2024 (actual)
- Study completion
- 10 Jun 2024 (actual)
- First posted
- 4 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| cirrhosis of the liver, stadium Child A | – | 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)sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
| cirrhosis of the liver, stadium Child B | – | 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)sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
| cirrhosis of the liver, stadium Child C | – | 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)sampling of biological material and health related data collection longitudinally in 6-monthly intervals up to 36 months |
| cirrhosis of the liver, acutely decompensated | – | 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)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 |
| acute 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)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 |
| healthy controls | – | Other: blood sampling for research purpose, Other: clinical data collection, Other: Health-related Questionnairessampling of biological material and health related data collection on day 1 (Baseline) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (3 listed)
- Patients with compensated or decompensated chronic liver disease
- Patients with acute- or acute-on-chronic chronic liver failure
- Controls with no liver disease
Key exclusion criteria (1 listed)
- Evidence of disseminated malignancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood sampling for research purposeblood sampling for research purpose (about 30ml) taken by venepuncture or from intravenous catheters if already in place | Other | 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 collectionclinical 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 | 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 QuestionnairesHealth-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 | 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 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. | Other | 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 |
Primary outcome
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
1 secondary outcome
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jun 2024.
Related trials for Liver Disease
Not yet recruitingPhase 1
Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
Colorectal Neoplasms, Neoplasms
Not yet recruitingObservational study
Prevalence and Development of Liver Dysfunction in Hematopoietic Stem Cell Transplant
Hematopoietic Stem Cell Transplant
Not yet recruitingObservational study
Periodontal Status and Biomarkers in MASLD
Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)
RecruitingObservational study
Effectiveness and Clinical Outcomes of Long-term Bulevirtide Monotherapy in Patients With HDV-related Compensated Cirrhosis
Hepatitis D
Active, not recruitingPhase 2
A Study of Sequential Therapy With Daplusiran/Tomligisiran (DAP/TOM) Followed by Bepirovirsen in Participants Living With Chronic Hepatitis B (CHB)
Chronic Hepatitis B Virus Infection, Hepatitis B
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Christine Bernsmeier, PD Dr. Dr. principal investigator
Universitätsspital Basel, Departement Biomedizin, Gastroenterologie und Hepatologie
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Disease and Cirrhosis of the Liver, run by University Hospital, Basel, Switzerland at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Switzerland, United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jun 2024.