Cirrhosis, LiverNCT05793983
S100A8/A9 and Innate Immunity in Liver Disease
An observational study of Cirrhosis, Liver and Immune Suppression, run by St George's, University of London at 1 site in United Kingdom.
Trial summary
This observational study evaluates the concentration of immune protein S100A8/A9 in different liver failure syndromes, its interaction with the immune system and validity as an immunotherapeutic target to improve survival in patients with advanced cirrhosis and/or acute on chronic liver failure. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Cirrhosis, Liver, Immune Suppression, Liver Failure, Acute on Chronic
- How many people
- 100 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Sep 2021to 1 Sep 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 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Primary population is patients with acute or chronic liver disease admitted to hospital (including intensive care unit) or out-patient setting. Control subjects includes patients with sepsis, patients without liver disease but on continuous ambulatory peritoneal dialysis for renal replacement therapy (ascites control) and healthy subjects.
Who may be able to join
- Patients with acute or chronic liver disease:
- Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings)
- Acute alcoholic hepatitis (definition as per Crabb et al, 2016)35
- Acute liver failure due to any aetiology
- Acute-on-chronic liver failure (defined as per EASL-CLIF definition)17
- Patients undergoing diagnostic or therapeutic abdominal paracentesis Patients with acute or chronic liver disease of any aetiology undergoing clinically-indicated paracentesis for ascites
Show all 21Show fewer
- Patients undergoing broncho-alveolar lavage
- Intubated patients with liver disease in intensive care
- Undergoing a bronchoscopy or a non-directed broncho-alveolar lavage as part of their routine clinical care
- Patients with acute or chronic liver disease undergoing liver biopsy (percutaneous or transjugular) as routine part of their clinical care
- Patients with portal hypertension (cirrhotic or non-cirrhotic) undergoing transjugular intrahepatic shunt (TIPSS) placement as part of their routine care
- Patients with acute or chronic liver disease undergoing orthoptic liver transplantation
- Patients undergoing surgical liver resection or hepatectomy for liver-related diseases
- Control groups:
- Patients with ascites without chronic liver disease:
- Absence of cirrhosis based on clinical, radiological or histopathological features, including patients with non-cirrhotic portal hypertension, cardiac ascites (ascites due to heart failure) or patients with chronic kidney disease undergoing continuous ambulatory peritoneal dialysis (CAPD)
- Presence of clinically significant ascites
- Undergoing diagnostic or therapeutic paracentesis
- Patients with sepsis without acute or chronic liver disease
- Patients with haemochromatosis without liver disease or end-organ damage who undergo regular venesection
- Healthy subjects
Who cannot join
- Age under 18 or over 80 Evidence of disseminated malignancy (isolated cancers including hepatocellular carcinoma are not an exclusion criteria) Patients with known immunodeficiency syndromes (e.g. HIV infection)
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Arjuna Singanayagam
Wandsworth, London, SW17 0RE
Arjuna Singanayagam, MBBS; PhD, 02086729944 ext. 30125, asingana@sgul.ac.uk
About this study
Official title: The Interaction of the S100A8/A9 Protein With the Innate Immune System in the Immunopathology of Acute and Chronic Liver Disease
This observational study evaluates the concentration of immune protein S100A8/A9 in different liver failure syndromes, its interaction with the immune system and validity as an immunotherapeutic target to improve survival in patients with advanced cirrhosis and/or acute on chronic liver failure.
Read the detailed description
A paradox exists in chronic liver disease whereby there is a general recognition that chronic inflammation is part of the pathophysiology, heightened when there is an acute deterioration and organ failure (acute-on-chronic liver failure), yet there is an increased susceptibility to infection due to a dysfunctional immune system, which is often the trigger for organ failure and the reason for death in these patients.
A danger signal reported in other inflammatory conditions called S100A8/A9 (calprotectin) is known to activate the immune system by production of pro-inflammatory cytokines but has also been observed to promote the development immunosuppressive signals (e.g. IL-10 and MDSCs).
In an attempt to explain this paradox in liver disease, this study proposes to identify at the cellular and molecular level, the triggers for S100A8/A9 production, how it varies with time in stable patients and those that have acute deteriorations including the development of organ failure, and its interaction with innate immune cells in the circulation and at tissue level.
By studying this, the Investigators hope to be able to identify immunotherapeutic targets and understand whether potential immunotherapy could be applied locally or systemically. The Investigators' observations in this study could provide the basis for the future development of clinical immunomodulating agents, which may ameliorate immunopathology, reduce susceptibility to infection and could reduce mortality in critically ill patients with liver disease. Findings in this study may also have more generalizable impact especially with the recent recognition in the COVID-19 pandemic that immunomodulatory therapies may improve the clinical outcomes of inflammatory phenotypes in virus-induced severe sepsis.
- Conditions
- Cirrhosis, Liver, Immune Suppression, Liver Failure, Acute on Chronic, Ascites Hepatic, Infections
- Keywords
- cirrhosis, acute-on-chronic liver failure, immune paralysis
- Medical subject headings
- Liver Cirrhosis, Acute-On-Chronic Liver Failure, Infections, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with acute or chronic liver disease | 1. Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings) 2. Acute alcoholic hepatitis 3. Acute liver failure due to any aetiology 4. Acute-on-chronic liver failure | |
| Patients undergoing diagnostic or therapeutic abdominal paracentesis | Patients with acute or chronic liver disease of any aetiology undergoing clinically-indicated paracentesis for ascites | |
| Patients undergoing broncho-alveolar lavage | 1. Intubated patients with liver disease in intensive care 2. Undergoing a bronchoscopy or a non-directed broncho-alveolar lavage as part of their routine clinical care | |
| Patients with acute or chronic liver disease undergoing liver biopsy | Not described | |
| Patients with undergoing transjugular intrahepatic shunt (TIPSS) placement | Not described | |
| Patients with acute or chronic liver disease undergoing orthoptic liver transplantation | Not described | |
| Patients undergoing surgical liver resection or hepatectomy for liver-related diseases | Not described | |
| Patients with ascites without chronic liver disease | 1. Absence of cirrhosis based on clinical, radiological or histopathological features, including patients with non-cirrhotic portal hypertension, cardiac ascites (ascites due to heart failure) or patients with chronic kidney disease undergoing continuous ambulatory peritoneal dialysis (CAPD) 2. Presence of clinically significant ascites 3. Undergoing diagnostic or therapeutic paracentesis | |
| Patients with sepsis without acute or chronic liver disease | Not described | |
| Patients with haemochromatosis who undergo regular venesection | Not described | |
| Healthy subjects | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of plasma S100A8/A9
The study will evaluate whether S100A8/A9 concentration can be used to predict clinical outcomes, such as mortality, the development of infection and/or organ failure. In the laboratory, it will evaluate the effect S100A8/A9 has on immune functional readouts including phagocytosis, oxidative burst and cytokine production, all of which are required for an effect immune response. Similarly, by blocking its action, the study will identify whether this is a potential immunotherapeutic strategy to improve the outcome of patients with high concentrations of the protein.
Measured: 1 years
Secondary outcomes (2)
Mortality
28-, 90-day and 1 year mortality and its relationship to baseline and serial S100A8/A9 concentration
Measured: 1 years
Development of infection
Incidence of infection in patients with liver disease and its relationship to baseline or dynamic S100A8/A9 concentration
Measured: 1 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Mar 2023
- Study start28 Sep 2021
- Primary completion1 Sep 2023 (estimated)
- Study completion1 Sep 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhosis, LiverStudies of the same condition, open and under way.
- 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
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- St George's, University of London
- Sponsor type
- University, hospital or other
- Collaborators
- King's College Hospital NHS Trust
- Responsible party
- Sponsor
- Investigators
- Arjuna Singanayagam, MBBS; PhD, Principal investigator, St George's, University of London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05793983
- Sponsor's protocol ID
- 2021.0073
- Other IDs
- 285573
- Status last verified
- Mar 2023
- First submitted
- 8 Oct 2021
- Last updated
- 31 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 31 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Interaction of the S100A8/A9 Protein With the Innate Immune System in the Immunopathology of Acute and Chronic Liver Disease
- ClinicalTrials.gov ID
- NCT05793983
- Acronym / sponsor ID
- 2021.0073
- Conditions
- Cirrhosis, Liver, Immune Suppression, Liver Failure, Acute on Chronic, Ascites Hepatic, Infections
- Keywords
- cirrhosis, acute-on-chronic liver failure, immune paralysis
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- St George's, University of LondonUniversity, hospital or other
- Collaborators
- King's College Hospital NHS Trust
- Study start
- 28 Sep 2021 (actual)
- Primary completion
- 1 Sep 2023 (estimated)
- Study completion
- 1 Sep 2024 (estimated)
- First posted
- 31 Mar 2023 (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 observational study evaluates the concentration of immune protein S100A8/A9 in different liver failure syndromes, its interaction with the immune system and validity as an immunotherapeutic target to improve survival in patients with advanced cirrhosis and/or acute on chronic liver failure.
Detailed description
A paradox exists in chronic liver disease whereby there is a general recognition that chronic inflammation is part of the pathophysiology, heightened when there is an acute deterioration and organ failure (acute-on-chronic liver failure), yet there is an increased susceptibility to infection due to a dysfunctional immune system, which is often the trigger for organ failure and the reason for death in these patients.
A danger signal reported in other inflammatory conditions called S100A8/A9 (calprotectin) is known to activate the immune system by production of pro-inflammatory cytokines but has also been observed to promote the development immunosuppressive signals (e.g. IL-10 and MDSCs).
In an attempt to explain this paradox in liver disease, this study proposes to identify at the cellular and molecular level, the triggers for S100A8/A9 production, how it varies with time in stable patients and those that have acute deteriorations including the development of organ failure, and its interaction with innate immune cells in the circulation and at tissue level.
By studying this, the Investigators hope to be able to identify immunotherapeutic targets and understand whether potential immunotherapy could be applied locally or systemically. The Investigators' observations in this study could provide the basis for the future development of clinical immunomodulating agents, which may ameliorate immunopathology, reduce susceptibility to infection and could reduce mortality in critically ill patients with liver disease. Findings in this study may also have more generalizable impact especially with the recent recognition in the COVID-19 pandemic that immunomodulatory therapies may improve the clinical outcomes of inflammatory phenotypes in virus-induced severe sepsis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 11
| Arm | Type | Receives |
|---|---|---|
| Patients with acute or chronic liver disease | – | –1. Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings) 2. Acute alcoholic hepatitis 3. Acute liver failure due to any aetiology 4. Acute-on-chronic liver failure |
| Patients undergoing diagnostic or therapeutic abdominal paracentesis | – | –Patients with acute or chronic liver disease of any aetiology undergoing clinically-indicated paracentesis for ascites |
| Patients undergoing broncho-alveolar lavage | – | –1. Intubated patients with liver disease in intensive care 2. Undergoing a bronchoscopy or a non-directed broncho-alveolar lavage as part of their routine clinical care |
| Patients with acute or chronic liver disease undergoing liver biopsy | – | – |
| Patients with undergoing transjugular intrahepatic shunt (TIPSS) placement | – | – |
| Patients with acute or chronic liver disease undergoing orthoptic liver transplantation | – | – |
| Patients undergoing surgical liver resection or hepatectomy for liver-related diseases | – | – |
| Patients with ascites without chronic liver disease | – | –1. Absence of cirrhosis based on clinical, radiological or histopathological features, including patients with non-cirrhotic portal hypertension, cardiac ascites (ascites due to heart failure) or patients with chronic kidney disease undergoing continuous ambulatory peritoneal dialysis (CAPD) 2. Presence of clinically significant ascites 3. Undergoing diagnostic or therapeutic paracentesis |
| Patients with sepsis without acute or chronic liver disease | – | – |
| Patients with haemochromatosis who undergo regular venesection | – | – |
| Healthy subjects | – | – |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Primary population is patients with acute or chronic liver disease admitted to hospital (including intensive care unit) or out-patient setting. Control subjects includes patients with sepsis, patients without liver disease but on continuous ambulatory peritoneal dialysis for renal replacement therapy (ascites control) and healthy subjects.
Key inclusion criteria (21 listed)
- Patients with acute or chronic liver disease:
- Presence of chronic liver disease, or cirrhosis due to any aetiology (latter based upon a histopathological diagnosis or compatible laboratory data and radiological findings)
- Acute alcoholic hepatitis (definition as per Crabb et al, 2016)35
- Acute liver failure due to any aetiology
- Acute-on-chronic liver failure (defined as per EASL-CLIF definition)17
Key exclusion criteria (1 listed)
- Age under 18 or over 80 Evidence of disseminated malignancy (isolated cancers including hepatocellular carcinoma are not an exclusion criteria) Patients with known immunodeficiency syndromes (e.g. HIV infection)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Concentration of plasma S100A8/A9
Time frame: 1 years
The study will evaluate whether S100A8/A9 concentration can be used to predict clinical outcomes, such as mortality, the development of infection and/or organ failure. In the laboratory, it will evaluate the effect S100A8/A9 has on immune functional readouts including phagocytosis, oxidative burst and cytokine production, all of which are required for an effect immune response. Similarly, by blocking its action, the study will identify whether this is a potential immunotherapeutic strategy to improve the outcome of patients with high concentrations of the protein.
2 secondary outcomes
Mortality
Time frame: 1 years
Development of infection
Time frame: 1 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Mar 2023.
- Individual participant dataSharing planned: No
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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.
Arjuna Singanayagam, MBBS; PhD principal investigator
St George's, University of London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cirrhosis, Liver and Immune Suppression, run by St George's, University of London at 1 site in United Kingdom.
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 21 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: status not confirmed, as of the sponsor's last update on 31 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Arjuna Singanayagam, MBBS; PhD (02086729944 ext. 30125, asingana@sgul.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of plasma S100A8/A9 (time frame: 1 years). 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 31 Mar 2023.