Congenital Heart DiseaseNCT05213598
Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
An observational study of Congenital Heart Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
Trial summary
Background: In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Congenital Heart Disease
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Sep 2022to 30 Jun 2051
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: male and female subjects >=18 years of age who historically underwent Fontan procedure due to a severe CHD and thus are at risk for FALD by virtue of their altered physiology
Who may be able to join
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Male and female subjects >= 18 years of age.
- Past surgical history of Fontan procedure.
- Prior enrollment in the Liver Diseases Branch protocol 91DK0214
- Underwent cardiac catheterization or transjugular liver biopsy within ten years prior to the date of screening
- Approved to proceed by the NIH Cardiology Consult
- Approved to proceed by the NIH Cardiac Pre-anesthesia Consult
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Evidence of other forms of liver disease that typically result in cirrhosis.
- Evidence of active Chronic Hepatitis B infection as defined by the presence of hepatitis B surface antigen (HBsAg) in serum and elevated HBV DNA (>10,000 IU/mL).
- Hepatitis C as defined by the presence of hepatitis C RNA in serum.
- Evidence of other liver disease such as primary sclerosing cholangitis, primary biliary cirrhosis, Wilson s disease, autoimmune hepatitis as defined by either liver histology or laboratory abnormalities.
- Hemochromatosis as defined by presence of 3+ or 4+ stainable iron on liver biopsy or homozygosity for C282Y. Patients with iron saturation indices of >45% and serum ferritin levels of >300 ng/ml for men and >250 ng/ml for women will undergo genetic testing for hemochromatosis.
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- Bile duct obstruction as suggested by imaging studies done within the previous six months.
- Active substance abuse, such as alcohol, inhaled or injection drugs within the previous one year (assessed during patient interviews or by patient self-report).
- Evidence of hepatocellular carcinoma; either alpha-fetoprotein (AFP) levels greater than 50 ng/ml (normal <6.6 ng/ml) and/or ultrasound (or other imaging study) demonstrating a mass suggestive of liver cancer.
- Evidence of Cholangiocarcinoma.
- A documented or otherwise stated severe allergic reaction to contrast.
- Any other severe condition, which in the opinion of the investigators would impede the patient s participation or compliance in the study.
- Radiation exposure exceeds 5 rems during the past year.
- Inability to comply or give written informed consent as there is no direct benefit from participation in this study.
- Female subjects who are currently pregnant will be excluded due to radiation exposure necessary for study completion. In addition, altered hemodynamics may confound the study s results. Following pregnancy, patients may be reconsidered for the study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR), 800-411-1222 ext. TTY dial 711, ccopr@nih.gov
About this study
Official title: Natural History of Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
Background:
In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it.
Read more
Objective:
To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis.
Eligibility:
People aged 18 and older who are at risk of developing FALD from the Fontan procedure.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Liver ultrasound. This uses sound waves to take pictures of the body.
Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit.
Visits will include repeats of the screening tests and:
Heart tests
Stool collection
Questionnaires
MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct.
Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver.
Upper endoscopy. This uses a thin scope to look inside the upper digestive tract.
Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.
Read the detailed description
Study Description:
Up to 100 subjects who completed the Fontan procedure for severe Congenital Heart Disease (CHD) and are at risk for congestive hepatopathy or Fontan Associated Liver Disease (FALD) will be offered inclusion in the study. During the study we will pursue novel biomarkers for disease severity.
Objectives:
Primary Objective:
The goal of this study is to globally investigate a large cohort of FALD subjects to generate an understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD. We will use our findings to generate novel biomarkers that will enable improved follow-up of subjects and enhance transplant decision making.
Secondary Objectives:
- Measurement of TGF-beta serum levels in Fontan subjects and comparing them to liver tissue biopsies in hope of pursuing a novel biomarker for the development of advanced FALD.
- Evaluation of FALD subjects coagulation profile including von Willebrand factor assessment and correlating it to disease severity by liver biopsy.
- Comparison of PAR-1 and PAR-2 receptor staining from liver tissue biopsies of Fontan subjects and corelate their presence to the severity of the subjects FALD.
- Identification of genetic modifiers of FALD
- Evaluation of hepatic transcriptome in various stages of FALD.
- Characterization of microbiome signatures in FALD
Endpoints:
Primary Endpoints:
- Identification of novel biomarkers correlating with disease progression markers in Fontan Associated Liver Disease.
- Develop an understanding of the biological mechanisms and the genetic modifiers of the progression of Fontan Associated Liver Disease.
Secondary Endpoints:
- TGF-beta superfamily measurement in serum and establishment of a cut-off level correlating with FALD severity.
- Complete coagulation profile measurement and vWF-Ag quantification with establishment of cut- offs correlating with FALD severity.
- PAR-1 and PAR-2 immuno-staining in Fontan subjects liver tissue biopsies.
- Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype.
- Identification of novel markers of fibrosis or the development of hepatic neoplasia from transcriptome analysis.
- Characterization of microbiome signatures (taxonomic and functional), as well as identification of specific species.
- Conditions
- Congenital Heart Disease
- Keywords
- Cardiac Hepatopathy, Natural History
- Medical subject headings
- Heart Defects, Congenital
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 |
|---|---|---|
| Adults with FALD | male and female subjects =18 years of age who historically underwent Fontan procedure due to a severe CHD and thus are at risk for FALD by virtue of their altered physiology |
What is being measured
The primary outcome is the main question the study is designed to answer.
To generate understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD
Identification of novel biomarkers correlating with disease progression markers in Fontan Associated Liver Disease Develop an understanding of the biological mechanisms and the genetic modifiers of the progression of Fontan Associated Liver Disease
Measured: End of Study
Secondary outcomes (6)
Comparison of PAR-1 and PAR-2 receptor staining from liver tissue biopsies of Fontan patients and corelate their presence to the severity of the patients FALD
PAR-1 and PAR-2 immuno-staining in Fontan subjects liver tissue biopsies
Measured: End of Study
Characterization of microbiome signatures in FALD
Characterization of microbiome signatures (taxonomic and functional), as well as identification of specific species
Measured: End of Study
Evaluation of hepatic transcriptome in various stages of FALD
Identification of novel markers of fibrosis or the development of hepatic neoplasia from transcriptome analysis
Measured: End of Study
Identification of genetic modifiers of FALD
Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype
Measured: End of Study
Measurement of TGF-? serum levels in Fontan subjects and comparing them to liver tissue biopsies in hope of pursuing a novel biomarker for the development of advanced FALD.
TGF-beta superfamily measurement in serum and establishment of a cut-off level correlating with FALD severity
Measured: End of Study
Evaluation of FALD patients coagulation profile including von Willebrand factor assessment and correlating it to disease severity by liver biopsy
Complete coagulation profile measurement and vWF-Ag quantification with establishment of cut- offs correlating with FALD severity
Measured: End of Study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start7 Sep 2022
- Primary completion30 Jun 2051 (estimated)
- Study completion30 Jun 2051 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- 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
- 100 participants (estimated)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Theo Heller, M.D., Principal investigator, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05213598
- Sponsor's protocol ID
- 10000494
- Other IDs
- 000494-DK
- Status last verified
- 8 Oct 2026
- First submitted
- 27 Jan 2022
- Last updated
- 13 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Human data generated in this research for future research as follows: De-identified data in an NIH-funded or approved public repository@@@@@@@@@@@@Data will be shared through: An NIH-funded or approved public repository.
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Natural History of Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
- ClinicalTrials.gov ID
- NCT05213598
- Acronym / sponsor ID
- 10000494
- Conditions
- Congenital Heart Disease
- Keywords
- Cardiac Hepatopathy, Natural History
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Study start
- 7 Sep 2022 (actual)
- Primary completion
- 30 Jun 2051 (estimated)
- Study completion
- 30 Jun 2051 (estimated)
- First posted
- 28 Jan 2022 (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.
Background:
In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it.
Objective:
To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis.
Eligibility:
People aged 18 and older who are at risk of developing FALD from the Fontan procedure.
Design:
Participants will be screened with:
Medical history
Physical exam
Blood and urine tests
Liver ultrasound. This uses sound waves to take pictures of the body.
Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit.
Visits will include repeats of the screening tests and:
Heart tests
Stool collection
Questionnaires
MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct.
Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver.
Upper endoscopy. This uses a thin scope to look inside the upper digestive tract.
Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.
Detailed description
Study Description:
Up to 100 subjects who completed the Fontan procedure for severe Congenital Heart Disease (CHD) and are at risk for congestive hepatopathy or Fontan Associated Liver Disease (FALD) will be offered inclusion in the study. During the study we will pursue novel biomarkers for disease severity.
Objectives:
Primary Objective:
The goal of this study is to globally investigate a large cohort of FALD subjects to generate an understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD. We will use our findings to generate novel biomarkers that will enable improved follow-up of subjects and enhance transplant decision making.
Secondary Objectives:
- Measurement of TGF-beta serum levels in Fontan subjects and comparing them to liver tissue biopsies in hope of pursuing a novel biomarker for the development of advanced FALD.
- Evaluation of FALD subjects coagulation profile including von Willebrand factor assessment and correlating it to disease severity by liver biopsy.
- Comparison of PAR-1 and PAR-2 receptor staining from liver tissue biopsies of Fontan subjects and corelate their presence to the severity of the subjects FALD.
- Identification of genetic modifiers of FALD
- Evaluation of hepatic transcriptome in various stages of FALD.
- Characterization of microbiome signatures in FALD
Endpoints:
Primary Endpoints:
- Identification of novel biomarkers correlating with disease progression markers in Fontan Associated Liver Disease.
- Develop an understanding of the biological mechanisms and the genetic modifiers of the progression of Fontan Associated Liver Disease.
Secondary Endpoints:
- TGF-beta superfamily measurement in serum and establishment of a cut-off level correlating with FALD severity.
- Complete coagulation profile measurement and vWF-Ag quantification with establishment of cut- offs correlating with FALD severity.
- PAR-1 and PAR-2 immuno-staining in Fontan subjects liver tissue biopsies.
- Establishment of positive or negative correlation between candidate susceptible genes and disease phenotype.
- Identification of novel markers of fibrosis or the development of hepatic neoplasia from transcriptome analysis.
- Characterization of microbiome signatures (taxonomic and functional), as well as identification of specific species.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Adults with FALD | – | –male and female subjects =18 years of age who historically underwent Fontan procedure due to a severe CHD and thus are at risk for FALD by virtue of their altered physiology |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- male and female subjects >=18 years of age who historically underwent Fontan procedure due to a severe CHD and thus are at risk for FALD by virtue of their altered physiology
Key inclusion criteria (7 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Male and female subjects >= 18 years of age.
- Past surgical history of Fontan procedure.
- Prior enrollment in the Liver Diseases Branch protocol 91DK0214
- Underwent cardiac catheterization or transjugular liver biopsy within ten years prior to the date of screening
Key exclusion criteria (15 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Evidence of other forms of liver disease that typically result in cirrhosis.
- Evidence of active Chronic Hepatitis B infection as defined by the presence of hepatitis B surface antigen (HBsAg) in serum and elevated HBV DNA (>10,000 IU/mL).
- Hepatitis C as defined by the presence of hepatitis C RNA in serum.
- Evidence of other liver disease such as primary sclerosing cholangitis, primary biliary cirrhosis, Wilson s disease, autoimmune hepatitis as defined by either liver histology or laboratory abnormalities.
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
To generate understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD
Time frame: End of Study
Identification of novel biomarkers correlating with disease progression markers in Fontan Associated Liver Disease Develop an understanding of the biological mechanisms and the genetic modifiers of the progression of Fontan Associated Liver Disease
6 secondary outcomes
Comparison of PAR-1 and PAR-2 receptor staining from liver tissue biopsies of Fontan patients and corelate their presence to the severity of the patients FALD
Time frame: End of Study
Characterization of microbiome signatures in FALD
Time frame: End of Study
Evaluation of hepatic transcriptome in various stages of FALD
Time frame: End of Study
Identification of genetic modifiers of FALD
Time frame: End of Study
Measurement of TGF-? serum levels in Fontan subjects and comparing them to liver tissue biopsies in hope of pursuing a novel biomarker for the development of advanced FALD.
Time frame: End of Study
Evaluation of FALD patients coagulation profile including von Willebrand factor assessment and correlating it to disease severity by liver biopsy
Time frame: End of Study
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Human data generated in this research for future research as follows: De-identified data in an NIH-funded or approved public repository@@@@@@@@@@@@Data will be shared through: An NIH-funded or approved public repository.
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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.
Theo Heller, M.D. principal investigator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Congenital Heart Disease, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 1 site in United States.
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 7 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Elenita M Rivera, R.N. ((301) 435-6125, erivera@cc.nih.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To generate understanding of how congestive hepatopathy drives the pathogenesis of cirrhosis in FALD (time frame: End of Study). 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 13 Oct 2026.