Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06392828 |
| Other study ID # |
PI-058 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
April 15, 2024 |
| Est. completion date |
December 31, 2025 |
Study information
| Verified date |
April 2024 |
| Source |
IMDEA Food |
| Contact |
Lidia Daimiel Ruiz, PhD |
| Phone |
+34917278100 |
| Email |
lidia.daimiel[@]alimentacion.imdea.org |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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 FLA>30
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).
