Non-Alcoholic Fatty Liver DiseaseEndo-NAFLDNCT06392828
EndoNAFLD: Relationship Between Fatty Liver Disease and Cardiovascular Diseases
An observational study of Non-Alcoholic Fatty Liver Disease and Cardiovascular Diseases, run by IMDEA Food at 4 sites in Spain.
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. Read more about this study
- Who is it for?
- Ages 50 to 69 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Cardiovascular Diseases
- How many people
- 63 participants
- Where
- 4 sitesSpain
- Study dates
- 15 Apr 2024to 19 Feb 2026
- 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 50 to 69 years
- All sexes
- Adult, Older adult
Study population: Patients attending internal medicine services from the collaborating hospitals will be invited to participate. Physicians responsible for their usual care will check inclusion/exclusion criteria before inviting them to participate. All participants are community-dwelling adults from Community of Madrid, Spain.
Who may be able to join
- Men and women
- 50-69 years old
- With CVD stratification according to ESC 2011 guidelines.
- With data to calculate NAFLD scores.
Who cannot join
- Type 1 or type 2 diabetes.
- Taking hypoglycemic drugs.
- Familiar hypercholesterolemia according to ESC criteria.
- Congenital defects on lipid metabolism.
- Taking hypolipidemic drugs targeting PCSK9.
- Participating on other clinical trials.
Show all 13Show fewer
- Chronic renal disease with filtration rate < 30 ml/min (RCD degree 4 KDIGO).
- Active cancer
- Liver disease no NAFLD.
- Von Willebrand disease or any other genetic condition with an impact on the plasma concentration of this biomarker.
- Systemic autoimmune disease.
- Uncapable of giving informed consent.
- Any other physical or cognitive condition that could affect the participation in the study.
Trial locations and contacts
4 sites in 1 country.
Spain4 sites
Clínica Universidad de Navarra
Madrid, Madrid, 28027
Hospital 12 de Octubre
Madrid, Madrid, 28041
Hospital Central de la Defensa Gomez Ulla
Madrid, Madrid, 28047
Hospital HM Montepríncipe
Madrid, Madrid, 28660
About this study
Official title: EndoNAFLD: Evaluation of the Relationship Between Fatty Liver Disease and Endothelial Damage in Patients at High Risk of Cardiovascular Disease
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.
Read more
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.
Read the 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 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).
- Keywords
- endothelial damage, microbiota, liver disease, fatty liver disease, NAFLD, MAFLD, cardiovascular disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Cardiovascular Diseases, Liver Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Group 1: no NAFLD, no prevalent CVD. | The aim of this group is to serve as control group. FLI <30 or hepatic echography negative for liver steatosis if FLI >30; FLI < 60, con SCORE2 < 5 % and no prevalent CVD according to ESC 202122. | |
| Group 2: NAFLD, no prevalent CVD | FLI >60 or hepatic echography positive for liver steatosis if FLI >30; FLI < 60, con SCORE2 > 5 % and no prevalent CVD according to ESC 202122. | |
| Group 3: no NAFLD, prevalent CVD | FLI <30 or hepatic echography negative for liver steatosis if FLI >30; FLI < 60, con SCORE2 < 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction). | |
| Group 4: NAFLD, prevalent CVD | FLI >60 or hepatic echography positive for liver steatosis if FLI >30; FLI < 60, con SCORE2 > 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction). |
What is being measured
The primary outcome is the main question the study is designed to answer.
Endothelial damage
Measure of plasma concentration of Von Willebrand Factor in UI/dL
Measured: 5 years
Endothelial damage
Measure of plasma concentration of Factor VIII in UI/mL
Measured: 5 years
Endothelial damage
Measure of plasma concentration of Tissue Factor in ng/mL
Measured: 5 years
Secondary outcomes (8)
Endothelial dysfunction
Measure of plasma concentration of ICAM and VCAM measured, both, in ng/mL
Measured: 5 years
Inflammatory status
Measure of plasma concentration of TNF-alpha, IL-1B and IL-6, measured in ng/mL
Measured: 5 years
Ketogenic metabolism
Measure of blood levels of beta-hydroxybutyrate
Measured: 5 years
Genomic profile
Measure of the relative expression, through Real-Time qPCR, of a panel of selected genes.
Measured: 5 years
MicroRNA profile
Measure of the relative expression, through Real-Time qPCR, of a panel of selected microRNAs.
Measured: 5 years
Microbiota diversity
Measure of alpha diversity and gut microbial composition through 16S sequencing of fecal samples.
Measured: 5 years
Microbiota functionality
Metagenomic analysis of microbiota genes by sequencing
Measured: 5 years
Cardiovascular disease incidence
Registration of major cardiovascular events (cardiovascular mortality, chest angina, accute myocardial infarction and stroke)
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Apr 2024
- Study start15 Apr 2024
- Primary completion19 Feb 2026
- Study completion19 Feb 2026
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 DiseaseStudies 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
- Prospective
- Enrolment
- 63 participants (actual)
Sponsor and investigators
- Lead sponsor
- IMDEA Food
- Sponsor type
- University, hospital or other
- Collaborators
- Sociedad Española de Arteriosclerosis, Clinica Universidad de Navarra, Universidad de Navarra, Hospital HM Montepríncipe, Hospital Central de la Defensa Gómez Ulla, Hospital Universitario 12 de Octubre
- Responsible party
- Principal investigator, Lidia Daimiel Ruiz, IMDEA Food
- Investigators
- Lidia Daimiel Ruiz, PhD, Principal investigator, Fundación IMDEA AlimentaciónDiego Martínez Urbistondo, PhD, Study chair, Clinica Universidad de Navarra, Universidad de Navarra
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06392828
- Sponsor's protocol ID
- PI-058
- Acronym
- Endo-NAFLD
- Status last verified
- Mar 2026
- First submitted
- 25 Apr 2024
- Last updated
- 25 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: IPD will no be available for other researchers. Study database can be accessible totally or partially upon request to study coordinator.
Study at a glance
From the registry record, last updated by the sponsor on 25 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EndoNAFLD: Evaluation of the Relationship Between Fatty Liver Disease and Endothelial Damage in Patients at High Risk of Cardiovascular Disease
- ClinicalTrials.gov ID
- NCT06392828
- Acronym / sponsor ID
- Endo-NAFLD / PI-058
- Keywords
- endothelial damage, microbiota, liver disease, fatty liver disease, NAFLD, MAFLD, cardiovascular disease
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 63 participants (actual)
- Lead sponsor
- IMDEA FoodUniversity, hospital or other
- Collaborators
- Sociedad Española de Arteriosclerosis, Clinica Universidad de Navarra, Universidad de Navarra, Hospital HM Montepríncipe, Hospital Central de la Defensa Gómez Ulla, Hospital Universitario 12 de Octubre
- Study start
- 15 Apr 2024 (actual)
- Primary completion
- 19 Feb 2026 (actual)
- Study completion
- 19 Feb 2026 (actual)
- First posted
- 30 Apr 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.
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.
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 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).
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Group 1: no NAFLD, no prevalent CVD. | – | –The aim of this group is to serve as control group. FLI <30 or hepatic echography negative for liver steatosis if FLI >30; FLI < 60, con SCORE2 < 5 % and no prevalent CVD according to ESC 202122. |
| Group 2: NAFLD, no prevalent CVD | – | –FLI >60 or hepatic echography positive for liver steatosis if FLI >30; FLI < 60, con SCORE2 > 5 % and no prevalent CVD according to ESC 202122. |
| Group 3: no NAFLD, prevalent CVD | – | –FLI <30 or hepatic echography negative for liver steatosis if FLI >30; FLI < 60, con SCORE2 < 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction). |
| Group 4: NAFLD, prevalent CVD | – | –FLI >60 or hepatic echography positive for liver steatosis if FLI >30; FLI < 60, con SCORE2 > 5 % and prevalent CVD (chest angina, stroke, acute coronary syndrome, accute myocardial infarction). |
Who may qualify
- Ages
- 50 to 69 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Patients attending internal medicine services from the collaborating hospitals will be invited to participate. Physicians responsible for their usual care will check inclusion/exclusion criteria before inviting them to participate. All participants are community-dwelling adults from Community of Madrid, Spain.
Key inclusion criteria (4 listed)
- Men and women
- 50-69 years old
- With CVD stratification according to ESC 2011 guidelines.
- With data to calculate NAFLD scores.
Key exclusion criteria (13 listed)
- Type 1 or type 2 diabetes.
- Taking hypoglycemic drugs.
- Familiar hypercholesterolemia according to ESC criteria.
- Congenital defects on lipid metabolism.
- Taking hypolipidemic drugs targeting PCSK9.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Endothelial damage
Time frame: 5 years
Measure of plasma concentration of Von Willebrand Factor in UI/dL
Endothelial damage
Time frame: 5 years
Measure of plasma concentration of Factor VIII in UI/mL
Endothelial damage
Time frame: 5 years
Measure of plasma concentration of Tissue Factor in ng/mL
8 secondary outcomes
Endothelial dysfunction
Time frame: 5 years
Inflammatory status
Time frame: 5 years
Ketogenic metabolism
Time frame: 5 years
Genomic profile
Time frame: 5 years
MicroRNA profile
Time frame: 5 years
Microbiota diversity
Time frame: 5 years
Microbiota functionality
Time frame: 5 years
Cardiovascular disease incidence
Time frame: 5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Mar 2026.
- Individual participant dataSharing planned: No. IPD will no be available for other researchers. Study database can be accessible totally or partially upon request to study coordinator.
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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.
Lidia Daimiel Ruiz, PhD principal investigator
Fundación IMDEA Alimentación
Diego Martínez Urbistondo, PhD study chair
Clinica Universidad de Navarra, Universidad de Navarra
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-Alcoholic Fatty Liver Disease and Cardiovascular Diseases, run by IMDEA Food at 4 sites in Spain.
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 4 inclusion and 13 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: finished, as of the sponsor's last update on 25 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endothelial damage (time frame: 5 years). The study lists 3 primary outcomes in all. 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 25 Mar 2026.