Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease (iGAL-AXIS)

NCT06623084 | Not Yet Recruiting

• 1 other identifier: 6804
• Study Type: observational
• Target: 132
• Locations: 0 countries
• Sites: N/A

Brief 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. 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.

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD); NASH - Nonalcoholic Steatohepatitis; Cirrhosis; Control Condition

Keywords

Platelets; Liver; Metabolomics; Microbiota

Outcome Measures

Primary Outcomes (1)

• 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).

  1 year

Study Arms (4)

NAFL GROUP

The investigators plan to recruit n=33 subjects with NAFLD

Other: Platelets characterization

NASH GROUP

The investigators plan to recruit n=33 subjects with histologically proven NASH

Other: Platelets characterization

Cirrhotic patients

The investigators plan to recruit n=33 subjects with metabolic non-viral cirrhosis

Other: Platelets characterization

Controls group

The investigators plan to recruit n=33 sex- and age-matched metabolically healthy volunteers (without NAFLD)

Other: Platelets characterization

Interventions

Platelets characterization OTHER

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.

Cirrhotic patients; Controls group; NAFL GROUP; NASH GROUP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• age\>18;
• NAFLD patients according to EASL Guidelines 2016.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Stefania Basili: lead
• University of Rome Tor Vergata: collaborator
• Catholic University of the Sacred Heart: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

The investigators plan to recruit n=33 subjects with NAFLD, n=33 subjects with histologically proven NASH and n=33 subjects with metabolic non-viral cirrhosis and n=33 sex- and age-matched metabolically healthy volunteers (without NAFLD)

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fibrosis

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Stefania Basili, MD

CONTACT

+390649972018; stefania.basili@uniroma1.it

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Internal medicine Stefania Basili

Study Record Dates

• First Submitted: September 30, 2024
• First Posted: October 2, 2024
• Study Start: September 30, 2024
• Primary Completion: March 12, 2025
• Study Completion: December 24, 2025
• Last Updated: October 4, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share