Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
Natural History of Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment
2 other identifiers
observational
100
1 country
1
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for all trials
Started Sep 2022
Longer than P75 for all trials
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 27, 2022
CompletedFirst Posted
Study publicly available on registry
January 28, 2022
CompletedStudy Start
First participant enrolled
September 7, 2022
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 30, 2051
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 30, 2051
February 23, 2026
February 19, 2026
28.8 years
January 27, 2022
February 20, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
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
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
End of Study
Characterization of microbiome signatures in FALD
End of Study
Evaluation of hepatic transcriptome in various stages of FALD
End of Study
Identification of genetic modifiers of FALD
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.
End of Study
- +1 more secondary outcomes
Study Arms (1)
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
Eligibility Criteria
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
You may qualify if:
- 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
You may not qualify if:
- 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.
- 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Theo Heller, M.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Central Study Contacts
Study Design
- Study Type
- observational
- Observational Model
- COHORT
- Time Perspective
- PROSPECTIVE
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 27, 2022
First Posted
January 28, 2022
Study Start
September 7, 2022
Primary Completion (Estimated)
June 30, 2051
Study Completion (Estimated)
June 30, 2051
Last Updated
February 23, 2026
Record last verified: 2026-02-19
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL
- Time Frame
- Date will be shared at the time of publication or shortly thereafter.
- Access Criteria
- PI will review requests for and approve outside collaborators under appropriate individual agreements.
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.