Ignite Creation Date:
2024-05-06 @ 8:27 PM
Last Modification Date:
2024-10-26 @ 3:28 PM
Study NCT ID:
NCT06392828
Status:
RECRUITING
Last Update Posted:
2024-05-01
First Post:
2024-04-25
Brief Title:
EndoNAFLD Relationship Between Fatty Liver Disease and Cardiovascular Diseases
Sponsor:
IMDEA Food
Organization:
IMDEA Food
Study Overview
Official Title:
EndoNAFLD Evaluation of the Relationship Between Fatty Liver Disease and Endothelial Damage in Patients at High Risk of Cardiovascular Disease
Status:
RECRUITING
Status Verified Date:
2024-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Endo-NAFLD
Brief Summary:
Management of risk factors is the primary approach to prevent cardiovascular disease CVD In this regard the accurate scoring of disease risk is fundamental Non-alcoholic fatty liver disease NAFLD has emerged recently as a potential mediator of CVD onset and progression The hypothesis is that NAFLD can be a predictive CVD risk factor independent of other classical and well-known risk factors
Preliminary epidemiological studies suggested that the fat infiltration in the liver mirrored the cardiometabolic status of the patient But recent studies postulate that NAFLD could be a potential independent predictor of vascular injury
The mechanisms that link liver function and endothelial damage include modulation of adipose tissue function lipid metabolism regulation or glycemic homeostasis among others But new mechanisms that could link NAFLD and ECV are emerging The synthesis of ketone bodies in the liver is closely related to the cardiovascular system function Ketone bodies can provide up to 50 of energy required by specific tissues Plasma concentration of β-hydroxybutyrate is a biomarker of NAFLD Plasma β-hydroxybutyrate and acetoacetate levels are also inversely associated with endothelial injury
Other biomarkers on endothelial damage like von Willebrand factor ICAM VCAM or coagulation factors Factor VIII can be used to stratify patients according to the risk of CVD The improvement in the sensitivity specificity and accuracy of scores such as FLI HIS and FIB-4 and non-invasive techniques such as elastography allow the study of the relationship between liver disease and other comorbidities
The aim is to evaluate the potential of NAFLD to stratify patients according to the risk of CVD and to investigate the molecular mechanisms linking NAFLD and CVD
Preliminary epidemiological studies suggested that the fat infiltration in the liver mirrored the cardiometabolic status of the patient But recent studies postulate that NAFLD could be a potential independent predictor of vascular injury
The mechanisms that link liver function and endothelial damage include modulation of adipose tissue function lipid metabolism regulation or glycemic homeostasis among others But new mechanisms that could link NAFLD and ECV are emerging The synthesis of ketone bodies in the liver is closely related to the cardiovascular system function Ketone bodies can provide up to 50 of energy required by specific tissues Plasma concentration of β-hydroxybutyrate is a biomarker of NAFLD Plasma β-hydroxybutyrate and acetoacetate levels are also inversely associated with endothelial injury
Other biomarkers on endothelial damage like von Willebrand factor ICAM VCAM or coagulation factors Factor VIII can be used to stratify patients according to the risk of CVD The improvement in the sensitivity specificity and accuracy of scores such as FLI HIS and FIB-4 and non-invasive techniques such as elastography allow the study of the relationship between liver disease and other comorbidities
The aim is to evaluate the potential of NAFLD to stratify patients according to the risk of CVD and to investigate the molecular mechanisms linking NAFLD and CVD
Detailed Description:
The hypothesis is that the prevalence of NAFLD and its degree evaluated with non-invasive techniques and biomarkers is an independent risk factor of cardiovascular disease and can be used in scoring systems to stratify patients according to CVD risk
The specific objectives are
O1 To define the association between NAFLD prevalence and degree and endothelial damage
The investigators will use non-invasive methods to determine the presence and degree of NAFLD FLI echography elastography FIB-4 NAFLD score and Hepamet and the investigators will compare plasma concentrations of endothelial damage biomarkers Von Willebrand Factor Factor VIII and Tissue Factor among NAFLD degrees
O2 To describe the role of hepatic ketogenic metabolism as mediator of endothelial damage
The investigators will correlate plasma concentrations of β-hydroxybutyrate and keto acetone with plasma concentrations of biomarkers of endothelial damage
O3 To compare the expression of genes and microRNAs involved in endothelial function and liver metabolism and inflammation biomarkers among groups
Liver metabolism is strictly regulated through the regulation of the expression of genes encoding metabolic enzymes responsible for the metabolic reactions and transporters of intermediate metabolites The expression of such genes also depends on epigenetic mechanisms like microRNAs Thus the investigators will compare the expression of a selected panel of genes and microRNAs in blood samples of participants according to the clinicopathological group The investigators will measure circulating microRNAs in plasma and cellular genes and microRNAs in the cellular fraction of the blood samples
O4 To determine the role of the microbiome as mediator of the link between NAFLD and CVD
The investigators will collect fecal samples from participants and the investigators will compare alpha diversity and composition of the gut microbiota of the volunteers of the different clinicopathological groups The investigators will also carry out comparative metagenomic studies
Objectives 1 to 4 will be developed through a cross-sectional study in the participants
O5 To associate NAFLD with the incidence of CVD events or changes in endothelial damage biomarkers
Recruited participants with or without prevalent CVD will be followed up for 5 years to evaluate if the prevalence of NAFLD is associated with the incidence of CVD major events cardiovascular mortality myocardial infarction stroke or chest angina
To develop this aim the investigators will carry out a longitudinal cohort study for 5 years Participants recruited in any of the 4 clinicopathological groups will be contacted annually for 5 years to collect clinical lifestyle and anthropometrical data They will be also submitted to usual care protocols for their pathologies Clinical records will be checked to assess the incidence of CVD events
The aim is to recruit 112 participants men and women 50-69 years old that will be segregated according to NAFLD and CVD status
Group 1 no NAFLD no prevalent CVD Group 2 NAFLD no prevalent CVD Group 3 no NAFLD prevalent CVD Group 4 NAFLD prevalent CVD No NAFLD is described as Fatty Liver Index FLI 30 or hepatic echography negative for liver steatosis if FLI 30 or FLI 60 con SCORE2 5
NAFLD is described as FLI 60 or hepatic echography positive for liver steatosis if FLA30 or FLI 60 con SCORE2 5
Prevalent CVD is defined according to ESC 2011 guidelines chest angina stroke acute coronary syndrome or acute myocardial infarction
The specific objectives are
O1 To define the association between NAFLD prevalence and degree and endothelial damage
The investigators will use non-invasive methods to determine the presence and degree of NAFLD FLI echography elastography FIB-4 NAFLD score and Hepamet and the investigators will compare plasma concentrations of endothelial damage biomarkers Von Willebrand Factor Factor VIII and Tissue Factor among NAFLD degrees
O2 To describe the role of hepatic ketogenic metabolism as mediator of endothelial damage
The investigators will correlate plasma concentrations of β-hydroxybutyrate and keto acetone with plasma concentrations of biomarkers of endothelial damage
O3 To compare the expression of genes and microRNAs involved in endothelial function and liver metabolism and inflammation biomarkers among groups
Liver metabolism is strictly regulated through the regulation of the expression of genes encoding metabolic enzymes responsible for the metabolic reactions and transporters of intermediate metabolites The expression of such genes also depends on epigenetic mechanisms like microRNAs Thus the investigators will compare the expression of a selected panel of genes and microRNAs in blood samples of participants according to the clinicopathological group The investigators will measure circulating microRNAs in plasma and cellular genes and microRNAs in the cellular fraction of the blood samples
O4 To determine the role of the microbiome as mediator of the link between NAFLD and CVD
The investigators will collect fecal samples from participants and the investigators will compare alpha diversity and composition of the gut microbiota of the volunteers of the different clinicopathological groups The investigators will also carry out comparative metagenomic studies
Objectives 1 to 4 will be developed through a cross-sectional study in the participants
O5 To associate NAFLD with the incidence of CVD events or changes in endothelial damage biomarkers
Recruited participants with or without prevalent CVD will be followed up for 5 years to evaluate if the prevalence of NAFLD is associated with the incidence of CVD major events cardiovascular mortality myocardial infarction stroke or chest angina
To develop this aim the investigators will carry out a longitudinal cohort study for 5 years Participants recruited in any of the 4 clinicopathological groups will be contacted annually for 5 years to collect clinical lifestyle and anthropometrical data They will be also submitted to usual care protocols for their pathologies Clinical records will be checked to assess the incidence of CVD events
The aim is to recruit 112 participants men and women 50-69 years old that will be segregated according to NAFLD and CVD status
Group 1 no NAFLD no prevalent CVD Group 2 NAFLD no prevalent CVD Group 3 no NAFLD prevalent CVD Group 4 NAFLD prevalent CVD No NAFLD is described as Fatty Liver Index FLI 30 or hepatic echography negative for liver steatosis if FLI 30 or FLI 60 con SCORE2 5
NAFLD is described as FLI 60 or hepatic echography positive for liver steatosis if FLA30 or FLI 60 con SCORE2 5
Prevalent CVD is defined according to ESC 2011 guidelines chest angina stroke acute coronary syndrome or acute myocardial infarction
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None