Ignite Creation Date:
2024-10-26 @ 3:41 PM
Last Modification Date:
2024-10-26 @ 3:41 PM
Study NCT ID:
NCT06623084
Status:
NOT_YET_RECRUITING
Last Update Posted:
None
First Post:
2024-09-30
Brief Title:
Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease iGAL-AXIS
Sponsor:
None
Organization:
None
Study Overview
Official Title:
Integrated Phenotyping of the Gut-plAtelet-Liver AXIS in the Progression of Chronic Liver Disease iGAL-AXIS
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
No
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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 cytokineschemokines 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
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
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None