Fatty Liver DiseaseTHESISNCT04191044
Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers (THESIS)
An observational study of Fatty Liver Disease, run by Instituto de Investigación Marqués de Valdecilla.
Trial summary
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in our environment. Preliminary data suggest that portal hypertension may exist in the initial phases of NAFLD due to mechanisms that have not yet been elucidated. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Fatty Liver Disease
- What is being tested?
- A complete cardiovascular and liver characterization will be carried out
- How many people
- 170 participants
- Where
- No sites listed yet
- Study dates
- 10 Jan 2020to 10 Jul 2020
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Non-alcoholic fatty liver disease.
Who may be able to join
- Age between 18 and 65 years.
- Clinical suspicion of NAFLD.
- Severe (controlled attenuation parameter (CAP) ≥330 dB/m) or mild steatosis (CAP: 298-317 dB / m), and FibroScan® grade 2 fibrosis (M probe: 7-9 kpa; XL probe: 5-7.5 kpa) in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus.
- Fibroscan® grade 3 or 4 fibrosis (M probe:> 9 kpa; XL probe:> 7.5 kpa).
- Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points).
- Signature of informed consent.
Who cannot join
- Concomitant liver disease and patients with acute on chronic liver failure.
- Excessive alcohol consumption (≥ 30 grams per day in men and ≥ 20 grams per day in women).
- Comorbidities (HIV infection, connective diseases, prothrombotic disorders) and/or drugs (didanosine, azathioprine, oxaliplatin) associated with the presence of idiopathic non-cirrhotic portal hypertension.
- Clinical history of cardiovascular disease (ischemic cardiomyopathy, atrial fibrillation, valvular defects, severe arterial hypertension, previous hospitalizations secondary to heart failure, cerebrovascular disease).
- Severe renal impairment, defined by creatinine clearance <15 ml/min/1.73m2.
- Any previous or current thrombosis in any venous territory.
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- Uncontrolled psychiatric illness
- Contraindication to liver biopsy or any of the complementary tests included in the project.
- Hepatocellular carcinoma that does not meet Milan criteria.
- Pregnancy or breastfeeding
- Significant comorbidities that entail a functional limitation and/or a life expectancy of less than 12 months.
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in our environment. Preliminary data suggest that portal hypertension may exist in the initial phases of NAFLD due to mechanisms that have not yet been elucidated. The clinical relevance of its development in these initial phases is unknown, while in more advanced phases new data are required to confirm the close relationship between portal hypertension and the risk of decompensation described in other etiologies. Likewise, the influence of fibrosis and portal hypertension on the cardiovascular risk of patients with NAFLD is unknown. The aim of the present multicenter project is to characterize the presence of portal hypertension and the mechanisms involved in its development in the different stages of NAFLD, to assess the association between the degree of portal hypertension and the development of portal hypertension-related complications, to know the early cardiovascular risk in the different stages of the disease, and to identify noninvasive biomarkers of the presence and severity of portal hypertension.
- Conditions
- Fatty Liver Disease
- Being tested
- A complete cardiovascular and liver characterization will be carried out
- Keywords
- Non-alcoholic fatty liver disease
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
A complete cardiovascular and liver characterization will be carried outOther
A complete cardiovascular and liver characterization will be carried out, including some supplementary tests with minimal risks (e.g. hemodynamic study). If any disease is detected, patients will be referred to the corresponding specialized care following the usual clinical practice.
| Study group | Role | What they receive |
|---|---|---|
| NAFLD with mild steatosis and grade <3 fibrosis in patients | NAFLD with mild steatosis and grade <3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus. Receives: Other: A complete cardiovascular and liver characterization will be carried out | |
| NAFLD with severe steatosis and grade <3 fibrosis in patients | NAFLD with severe steatosis and grade <3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus. Receives: Other: A complete cardiovascular and liver characterization will be carried out | |
| NAFLD with advanced fibrosis | NAFLD with advanced fibrosis (i.e. grade 3 or 4 fibrosis) without previous portal hypertension-related complications Receives: Other: A complete cardiovascular and liver characterization will be carried out | |
| Decompensated NAFLD cirrhosis | Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points) Receives: Other: A complete cardiovascular and liver characterization will be carried out |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension
Measured: 1 months
Number of patients with NAFLD and advanced fibrosis with portal hypertension
Measured: 1 months
number of the mechanisms responsible for the appearance of portal hypertension by specifically assessing the following
An increase in sinusoidal vascular resistance and the relative importance of its structural (sinusoidal compression) and functional (endothelial dysfunction and activation of starry cells) components, Splanchnic vasodilatation leading to portal hyperflow and hyperdynamic circulation, proinflammatory state and Activation of angiogenesis.
Measured: 1 months
Threshold of portal hypertension leading to portal hypertension-related complications in patients with NAFLD
Measured: 1months
Secondary outcomes (2)
Impact of portal hypertension and hepatic fibrosis on early cardiovascular risk and the degree of liver and kidney function.
Measured: 1 months
Non-invasive biomarkers of the presence and severity of portal hypertension through metabolomics, extracellular vesicles and / or other analytical markers
liquid biopsy
Measured: 1 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2019
- Study start10 Jan 2020 (estimated)
- Primary completion10 Jan 2020 (estimated)
- Study completion10 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for 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
- Other
- Time perspective
- Prospective
- Enrolment
- 170 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Instituto de Investigación Marqués de Valdecilla
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Universitario Ramon y Cajal, Hospital General Universitario Gregorio Marañon, Puerta de Hierro University Hospital
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04191044
- Sponsor's protocol ID
- THESIS
- Acronym
- THESIS
- Status last verified
- Dec 2019
- First submitted
- 5 Dec 2019
- Last updated
- 12 Dec 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Baffy G. Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2018 Mar;63(3):563-576. doi: 10.1007/s10620-017-4903-5. Epub 2018 Jan 22.
PubMed 29368124Francque S, Verrijken A, Mertens I, Hubens G, Van Marck E, Pelckmans P, Van Gaal L, Michielsen P. Noncirrhotic human nonalcoholic fatty liver disease induces portal hypertension in relation to the histological degree of steatosis. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1449-57. doi: 10.1097/MEG.0b013e32833f14a1.
PubMed 21389796Mendes FD, Suzuki A, Sanderson SO, Lindor KD, Angulo P. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012 Sep;10(9):1028-33.e2. doi: 10.1016/j.cgh.2012.05.008. Epub 2012 May 18.
PubMed 22610002Rodrigues SG, Montani M, Guixe-Muntet S, De Gottardi A, Berzigotti A, Bosch J. Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis. Clin Gastroenterol Hepatol. 2019 Sep;17(10):2101-2109.e1. doi: 10.1016/j.cgh.2018.12.038. Epub 2019 Jan 6.
PubMed 30625404
Study at a glance
From the registry record, last updated by the sponsor on 12 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Portal Hypertension in Non-alcoholic Fatty Liver Disease: Association With Cardiovascular Risk and Identification of Non-invasive Biomarkers
- ClinicalTrials.gov ID
- NCT04191044
- Acronym / sponsor ID
- THESIS / THESIS
- Conditions
- Fatty Liver Disease
- Keywords
- Non-alcoholic fatty liver disease
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 170 participants (estimated)
- Lead sponsor
- Instituto de Investigación Marqués de ValdecillaUniversity, hospital or other
- Collaborators
- Hospital Universitario Ramon y Cajal, Hospital General Universitario Gregorio Marañon, Puerta de Hierro University Hospital
- Study start
- 10 Jan 2020 (estimated)
- Primary completion
- 10 Jan 2020 (estimated)
- Study completion
- 10 Jul 2020 (estimated)
- First posted
- 9 Dec 2019 (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.
Non-alcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver disease in our environment. Preliminary data suggest that portal hypertension may exist in the initial phases of NAFLD due to mechanisms that have not yet been elucidated. The clinical relevance of its development in these initial phases is unknown, while in more advanced phases new data are required to confirm the close relationship between portal hypertension and the risk of decompensation described in other etiologies. Likewise, the influence of fibrosis and portal hypertension on the cardiovascular risk of patients with NAFLD is unknown. The aim of the present multicenter project is to characterize the presence of portal hypertension and the mechanisms involved in its development in the different stages of NAFLD, to assess the association between the degree of portal hypertension and the development of portal hypertension-related complications, to know the early cardiovascular risk in the different stages of the disease, and to identify noninvasive biomarkers of the presence and severity of portal hypertension.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| NAFLD with mild steatosis and grade <3 fibrosis in patients | – | Other: A complete cardiovascular and liver characterization will be carried outNAFLD with mild steatosis and grade <3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus. |
| NAFLD with severe steatosis and grade <3 fibrosis in patients | – | Other: A complete cardiovascular and liver characterization will be carried outNAFLD with severe steatosis and grade <3 fibrosis in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus. |
| NAFLD with advanced fibrosis | – | Other: A complete cardiovascular and liver characterization will be carried outNAFLD with advanced fibrosis (i.e. grade 3 or 4 fibrosis) without previous portal hypertension-related complications |
| Decompensated NAFLD cirrhosis | – | Other: A complete cardiovascular and liver characterization will be carried outDecompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Non-alcoholic fatty liver disease.
Key inclusion criteria (6 listed)
- Age between 18 and 65 years.
- Clinical suspicion of NAFLD.
- Severe (controlled attenuation parameter (CAP) ≥330 dB/m) or mild steatosis (CAP: 298-317 dB / m), and FibroScan® grade 2 fibrosis (M probe: 7-9 kpa; XL probe: 5-7.5 kpa) in patients with grade 1 or 2 obesity and insulin resistance (HOMA index> 2.6) or diabetes mellitus.
- Fibroscan® grade 3 or 4 fibrosis (M probe:> 9 kpa; XL probe:> 7.5 kpa).
- Decompensated NAFLD cirrhosis (i.e. development of ascites, variceal hemorrhage, and/or hepatic encephalopathy) up to Child B (9 points).
Key exclusion criteria (11 listed)
- Concomitant liver disease and patients with acute on chronic liver failure.
- Excessive alcohol consumption (≥ 30 grams per day in men and ≥ 20 grams per day in women).
- Comorbidities (HIV infection, connective diseases, prothrombotic disorders) and/or drugs (didanosine, azathioprine, oxaliplatin) associated with the presence of idiopathic non-cirrhotic portal hypertension.
- Clinical history of cardiovascular disease (ischemic cardiomyopathy, atrial fibrillation, valvular defects, severe arterial hypertension, previous hospitalizations secondary to heart failure, cerebrovascular disease).
- Severe renal impairment, defined by creatinine clearance <15 ml/min/1.73m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| A complete cardiovascular and liver characterization will be carried outA complete cardiovascular and liver characterization will be carried out, including some supplementary tests with minimal risks (e.g. hemodynamic study). If any disease is detected, patients will be referred to the corresponding specialized care following the usual clinical practice. | Other | Decompensated NAFLD cirrhosis, NAFLD with advanced fibrosis, NAFLD with mild steatosis and grade <3 fibrosis in patients, NAFLD with severe steatosis and grade <3 fibrosis in patients |
Primary outcome
Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension
Time frame: 1 months
Number of patients with NAFLD and advanced fibrosis with portal hypertension
Time frame: 1 months
number of the mechanisms responsible for the appearance of portal hypertension by specifically assessing the following
Time frame: 1 months
An increase in sinusoidal vascular resistance and the relative importance of its structural (sinusoidal compression) and functional (endothelial dysfunction and activation of starry cells) components, Splanchnic vasodilatation leading to portal hyperflow and hyperdynamic circulation, proinflammatory state and Activation of angiogenesis.
Threshold of portal hypertension leading to portal hypertension-related complications in patients with NAFLD
Time frame: 1months
2 secondary outcomes
Impact of portal hypertension and hepatic fibrosis on early cardiovascular risk and the degree of liver and kidney function.
Time frame: 1 months
Non-invasive biomarkers of the presence and severity of portal hypertension through metabolomics, extracellular vesicles and / or other analytical markers
Time frame: 1 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Dec 2019.
- Background: PubMed 29368124Baffy G. Origins of Portal Hypertension in Nonalcoholic Fatty Liver Disease. Dig Dis Sci. 2018 Mar;63(3):563-576. doi: 10.1007/s10620-017-4903-5. Epub 2018 Jan 22.
- Background: PubMed 21389796Francque S, Verrijken A, Mertens I, Hubens G, Van Marck E, Pelckmans P, Van Gaal L, Michielsen P. Noncirrhotic human nonalcoholic fatty liver disease induces portal hypertension in relation to the histological degree of steatosis. Eur J Gastroenterol Hepatol. 2010 Dec;22(12):1449-57. doi: 10.1097/MEG.0b013e32833f14a1.
- Background: PubMed 22610002Mendes FD, Suzuki A, Sanderson SO, Lindor KD, Angulo P. Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2012 Sep;10(9):1028-33.e2. doi: 10.1016/j.cgh.2012.05.008. Epub 2012 May 18.
- Background: PubMed 30625404Rodrigues SG, Montani M, Guixe-Muntet S, De Gottardi A, Berzigotti A, Bosch J. Patients With Signs of Advanced Liver Disease and Clinically Significant Portal Hypertension Do Not Necessarily Have Cirrhosis. Clin Gastroenterol Hepatol. 2019 Sep;17(10):2101-2109.e1. doi: 10.1016/j.cgh.2018.12.038. Epub 2019 Jan 6.
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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.
Questions about this trial
What is this clinical trial studying?
An observational study of Fatty Liver Disease, run by Instituto de Investigación Marqués de Valdecilla.
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 6 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 12 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jose Ignacio Fortea (+34 942 204084, jifortea@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with NAFLD without advanced fibrosis and severe steatosis with portal hypertension (time frame: 1 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04191044, which also lists 4 linked publications.
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 12 Dec 2019.