Non-alcoholic Fatty Liver Disease (NAFLD)NCT06623084
Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease (iGAL-AXIS)
An observational study of Non-alcoholic Fatty Liver Disease (NAFLD) and NASH - Nonalcoholic Steatohepatitis, run by Stefania Basili.
Trial summary
Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD), NASH - Nonalcoholic Steatohepatitis, Cirrhosis
- What is being tested?
- Platelets characterization
- How many people
- 132 participants
- Where
- No sites listed yet
- Study dates
- 30 Sep 2024to 24 Dec 2025
- 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: A total of 132 individuals (n=33 subjects with NAFLD, n=33 subjects with histologically proven NASH and n=33 subjects with metabolic non-viral cirrhosis and n=33 healthy volunteers (without NAFLD) will be enrolled at the Policlinico Umberto I-Sapienza University of Rome, defined according to the EASL Guidelines 2016.
Who may be able to join
- age\>18;
- NAFLD patients according to EASL Guidelines 2016.
Who cannot join
- decompensated cirrhosis, other causes of chronic liver disease (infectious and immune-mediated); malabsorption syndromes (i.e., celiac disease, food allergy, small bowel bacterial overgrowth);
- inflammatory bowel disease; previous GI surgery;
- immunodeficiencies; neurological handicaps;
- use of NSAIDs, antibiotics, probiotics, or anti-secretory drugs within the 2 months preceding enrollment;
- abnormality of hemostasis and thrombosis; malignancies.
Trial locations and contacts
No sites are listed yet.
About this study
Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Combined stimuli from leukocytes and platelets would then lead to metabolic reprogramming of hepatocytes, progression to NASH and eventually cirrhosis.
To test this hypothesis, the investigators propose 2 objectives. Primary objective: To identify platelet features that correlate with liver disease progression.
Secondary objective: To study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver diseases and is now considered a global health problem. NAFLD is a spectrum of diseases ranging from simple hepatic steatosis (NAFL) to non-alcoholic Steatohepatitis (NASH). Over time, NAFLD may progress to cirrhosis and ultimately to hepatocellular carcinoma (HCC). The gold-standard for diagnosis is liver biopsy that allows to discriminate different types of steatosis, characterized by the accumulation of lipid droplets of different sizes in hepatocytes, with the largest droplets associated with the development of fibrosis and the severity of the disease. Future studies are needed to identify non- invasive diagnostic approaches alternative to liver biopsy. NAFLD is not considered a "hepato-centric" condition anymore. Bi-directional metabolic and immune lanes of communication with other organs, such as the gut, have been decoded. Gut dysbiosis, increased gut permeability and bacterial translocation within portal circulation have been reported in NAFLD, suggesting that the gut-liver axis represents a source of systemic and hepatic inflammation.
Many studies suggest that platelets may be the link between gut and liver dysfunction. Beyond their role in hemostasis platelets can sense PAMPs and DAMPs and actively participate in the inflammatory response and in tissue remodeling, by releasing bioactive molecules and by interacting with leukocytes. Gut-derived metabolites and bacterial endotoxins promote platelet hyper-reactivity and recent studies point to an important role of platelets in regulating chronic liver inflammation. Platelet-derived cytokines, such as TGF-β, PDGF-β and CXCL4 promote hepatic fibrosis, and platelet count has been used as a surrogate marker of liver fibrosis FIB-4 index). Platelet number and platelet aggregates are increased in liver sinusoids of NASH patients and colocalise with neutrophil extracellular traps (NETs). In mice it was shown that platelet colonization of the liver is a critical step for the recruitment of CD8+ T cells and NKT cells, which drive NASH progression through the release of cytokines and the metabolic reprogramming of hepatocytes. In humans, inhibition of platelets with a combination of aspirin and clopidogrel has been shown to reduce the development of NASH and subsequent progression to cirrhosis and HCC. Mechanistic insights suggest that the role of platelets in NAFLD progression is mediated through the interaction with immune cells.
- Conditions
- Non-alcoholic Fatty Liver Disease (NAFLD), NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Control Condition
- Being tested
- Platelets characterization
- Keywords
- Platelets, Liver, Metabolomics, Microbiota
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Platelets characterizationOther
To identify platelet features that correlate with liver disease progression and to study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.
| Study group | Role | What they receive |
|---|---|---|
| NAFL GROUP | The investigators plan to recruit n=33 subjects with NAFLD Receives: Other: Platelets characterization | |
| NASH GROUP | The investigators plan to recruit n=33 subjects with histologically proven NASH Receives: Other: Platelets characterization | |
| Cirrhotic patients | The investigators plan to recruit n=33 subjects with metabolic non-viral cirrhosis Receives: Other: Platelets characterization | |
| Controls group | The investigators plan to recruit n=33 sex- and age-matched metabolically healthy volunteers (without NAFLD) Receives: Other: Platelets characterization |
What is being measured
The primary outcome is the main question the study is designed to answer.
Inflammatory profiling
To compare the systemic inflammatory state of patients at different stages of liver disease, serum samples will be used to quantify the concentration of 13 inflammatory cytokines (pg/ml), including IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33, by multiplex bead-based flow cytometric assay. Moreover, serum samples will be analysed by standard ELISA for the presence of HMGB1 and calprotectin (MRP8/14), inflammatory biomarkers that are associated with liver disease progression, and for the presence of DNA-myeloperoxidase complexes that are specific markers of neutrophil extracellular traps (NETs).
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2024
- Study start30 Sep 2024 (estimated)
- Primary completion12 Mar 2025 (estimated)
- Study completion24 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies 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
- Cross-sectional
- Enrolment
- 132 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stefania Basili
- Sponsor type
- University, hospital or other
- Collaborators
- University of Rome Tor Vergata, Catholic University of the Sacred Heart
- Responsible party
- Sponsor-investigator, Stefania Basili, University of Roma La Sapienza
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06623084
- Sponsor's protocol ID
- 6804
- Status last verified
- Sep 2024
- First submitted
- 30 Sep 2024
- Last updated
- 4 Oct 2024
- 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 4 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease (iGAL-AXIS)
- ClinicalTrials.gov ID
- NCT06623084
- Acronym / sponsor ID
- 6804
- Conditions
- Non-alcoholic Fatty Liver Disease (NAFLD), NASH - Nonalcoholic Steatohepatitis, Cirrhosis, Control Condition
- Keywords
- Platelets, Liver, Metabolomics, Microbiota
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 132 participants (estimated)
- Lead sponsor
- Stefania BasiliUniversity, hospital or other
- Collaborators
- University of Rome Tor Vergata, Catholic University of the Sacred Heart
- Study start
- 30 Sep 2024 (estimated)
- Primary completion
- 12 Mar 2025 (estimated)
- Study completion
- 24 Dec 2025 (estimated)
- First posted
- 2 Oct 2024 (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.
Objective of the study Our working hypothesis is that platelets activated by gut-derived metabolites dock in the liver of NAFLD patients and amplify the inflammatory state by releasing pro-inflammatory cytokines/chemokines, which in turn recruit and activate leukocytes in the liver sinusoids. Combined stimuli from leukocytes and platelets would then lead to metabolic reprogramming of hepatocytes, progression to NASH and eventually cirrhosis.
To test this hypothesis, the investigators propose 2 objectives. Primary objective: To identify platelet features that correlate with liver disease progression.
Secondary objective: To study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is the main cause of chronic liver diseases and is now considered a global health problem. NAFLD is a spectrum of diseases ranging from simple hepatic steatosis (NAFL) to non-alcoholic Steatohepatitis (NASH). Over time, NAFLD may progress to cirrhosis and ultimately to hepatocellular carcinoma (HCC). The gold-standard for diagnosis is liver biopsy that allows to discriminate different types of steatosis, characterized by the accumulation of lipid droplets of different sizes in hepatocytes, with the largest droplets associated with the development of fibrosis and the severity of the disease. Future studies are needed to identify non- invasive diagnostic approaches alternative to liver biopsy. NAFLD is not considered a "hepato-centric" condition anymore. Bi-directional metabolic and immune lanes of communication with other organs, such as the gut, have been decoded. Gut dysbiosis, increased gut permeability and bacterial translocation within portal circulation have been reported in NAFLD, suggesting that the gut-liver axis represents a source of systemic and hepatic inflammation.
Many studies suggest that platelets may be the link between gut and liver dysfunction. Beyond their role in hemostasis platelets can sense PAMPs and DAMPs and actively participate in the inflammatory response and in tissue remodeling, by releasing bioactive molecules and by interacting with leukocytes. Gut-derived metabolites and bacterial endotoxins promote platelet hyper-reactivity and recent studies point to an important role of platelets in regulating chronic liver inflammation. Platelet-derived cytokines, such as TGF-β, PDGF-β and CXCL4 promote hepatic fibrosis, and platelet count has been used as a surrogate marker of liver fibrosis FIB-4 index). Platelet number and platelet aggregates are increased in liver sinusoids of NASH patients and colocalise with neutrophil extracellular traps (NETs). In mice it was shown that platelet colonization of the liver is a critical step for the recruitment of CD8+ T cells and NKT cells, which drive NASH progression through the release of cytokines and the metabolic reprogramming of hepatocytes. In humans, inhibition of platelets with a combination of aspirin and clopidogrel has been shown to reduce the development of NASH and subsequent progression to cirrhosis and HCC. Mechanistic insights suggest that the role of platelets in NAFLD progression is mediated through the interaction with immune cells.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NAFL GROUP | – | Other: Platelets characterizationThe investigators plan to recruit n=33 subjects with NAFLD |
| NASH GROUP | – | Other: Platelets characterizationThe investigators plan to recruit n=33 subjects with histologically proven NASH |
| Cirrhotic patients | – | Other: Platelets characterizationThe investigators plan to recruit n=33 subjects with metabolic non-viral cirrhosis |
| Controls group | – | Other: Platelets characterizationThe investigators plan to recruit n=33 sex- and age-matched metabolically healthy volunteers (without NAFLD) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 132 individuals (n=33 subjects with NAFLD, n=33 subjects with histologically proven NASH and n=33 subjects with metabolic non-viral cirrhosis and n=33 healthy volunteers (without NAFLD) will be enrolled at the Policlinico Umberto I-Sapienza University of Rome, defined according to the EASL Guidelines 2016.
Key inclusion criteria (2 listed)
- age\>18;
- NAFLD patients according to EASL Guidelines 2016.
Key exclusion criteria (5 listed)
- decompensated cirrhosis, other causes of chronic liver disease (infectious and immune-mediated); malabsorption syndromes (i.e., celiac disease, food allergy, small bowel bacterial overgrowth);
- inflammatory bowel disease; previous GI surgery;
- immunodeficiencies; neurological handicaps;
- use of NSAIDs, antibiotics, probiotics, or anti-secretory drugs within the 2 months preceding enrollment;
- abnormality of hemostasis and thrombosis; malignancies.
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 |
|---|---|---|
| Platelets characterizationTo identify platelet features that correlate with liver disease progression and to study the mechanistic relationship between gut dysbiosis, metabolome composition, inflammation, and platelet activation in chronic liver disease. | Other | Cirrhotic patients, Controls group, NAFL GROUP, NASH GROUP |
Primary outcome
Inflammatory profiling
Time frame: 1 year
To compare the systemic inflammatory state of patients at different stages of liver disease, serum samples will be used to quantify the concentration of 13 inflammatory cytokines (pg/ml), including IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1 (CCL2), IL-6, IL-8 (CXCL8), IL-10, IL-12p70, IL-17A, IL-18, IL-23, and IL-33, by multiplex bead-based flow cytometric assay. Moreover, serum samples will be analysed by standard ELISA for the presence of HMGB1 and calprotectin (MRP8/14), inflammatory biomarkers that are associated with liver disease progression, and for the presence of DNA-myeloperoxidase complexes that are specific markers of neutrophil extracellular traps (NETs).
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2024.
- 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.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-alcoholic Fatty Liver Disease (NAFLD) and NASH - Nonalcoholic Steatohepatitis, run by Stefania Basili.
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 2 inclusion and 5 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 4 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
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 Stefania Basili, MD (+390649972018 ext. +39, stefania.basili@uniroma1.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammatory profiling (time frame: 1 year). 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 4 Oct 2024.