Liver Disease, Myocardial Fibrosis and Collaterals in the Adult Fontan Patient a Metabolomics and Proteomics Approach

Liver Disease, Myocardial Fibrosis and Collaterals in the Adult Fontan Patient - a Metabolomics and Proteomics Approach

Out objective is to identify the mechanisms that promote hepatic and myocardial fibrosis, and collateral vessel formation in patients with complex congenital heart disease and Fontan circulation.

Study Overview

• Status: Recruiting
• Conditions: Liver Diseases; Myocardial Fibrosis; Heart Defects, Congenital; Patient Participation; Collateral Circulation, Any Site

Detailed Description

In their prior works the investigators could show that there is evidence of a proinflammatory condition in a certain subgroup of patients with complex congenital heart disease and a so called Fontan circulation. Those patients are also prone to develop hepatic and myocardial fibrosis as well as to reveal collateral vessel formation. The investigators' hypothesis is that this pro-inflammatory condition is not only reflecting pre-stages of one or more of those 3 issues, but that this is also a main driving mechanism to develop and hepatic or myocardial fibrosis and collateral vessels.

The objective of the here proposed study thus is to identify the mechanisms that promote hepatic and myocardial fibrosis, and collateral vessel formation, and thus provide insight into the determination of those Fontan patients that tend to develop those conditions. The investigators attempt to link the issues of hepatic and myocardial fibrosis and collateral vessel formation by directing our focus on the phospholipid, amino acid and bile acid metabolism and on cell surface markers, cytokines, and chemokines as surrogates for proinflammatory, profibrotic and proangiogenic conditions.

This study would thereby allow for a deeper insight into Fontan pathophysiology and sequelae and might provide first steps towards the identification of possible diagnostic or eventually therapeutic targets.

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Maria-Miriam Michel, MD; Phone Number: +436606862227; Email: miriam.michel@i-med.ac.at

Study Locations

• Austria
  • Innsbruck, Austria
    • Recruiting
    • Medical University of Innsbruck
    • Contact: Miriam Michel; Phone Number: +436606862227; Email: miriam.michel@i-med.ac.at
    • Contact: Phone Number: +436606862227

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Adult patients with Fontan circulation, see inclusion criteria. Healthy, biventrucal age- and sex-matched controls.

Description

Inclusion Criteria:

• written informed consent of participants
• age at testing of ≥18 years
• 8 h fasting before blood sampling
• Fontan circulation (patients)
• biventricular heart without structural or functional abnormality (controls)

Exclusion Criteria:

• Protein losing enteropathy (PLE) (patients are defined as "PLE positive" if there is/are serum protein <5g/dL and serum albumin <3g/dL (duration for more than 3 months and exclusion of other causes for hypoproteinemia) and documented enteric protein loss: faecal alpha-1-antitrypsin ≥400 µg/g
• medication directly affecting metabolic state, such as cholesterol-lowering agents, or haemodynamic state, such as beta-blockers or sildenafil, with the exception of angiotensin converting enzyme inhibitors, diuretics, and anticoagulants
• atrial or ventricular arrhythmia
• coronary artery disease (history of myocardial infarction, myocardial revascularisation, percutaneous coronary intervention, or coronary artery bypass surgery)
• any metabolic disease, such as diabetes mellitus
• malignancy
• obesity (body mass index (BMI) >25 kg/m2)
• underweight (BMI < 18 kg/m2)
• renal disease
• inflammatory disease such as acute or chronic infection
• myeloproliferative disorder
• pregnancy or lactation
• malnourishment
• mental handicap not allowing valid consent to participation in the study or CMR
• need of sedation or general anesthesia for CMR
• typical contraindications for performing CMR such as metal-containing mechanical or electronic implants
• claustrophobia

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patients; Patients with Fontan circulation. No intervention planned (observational study)
Controls; Healthy, biventricular controls. No intervention planned (observational study)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants	When aspired number of participants is reached	July 2021-December 2023

Collaborators and Investigators

• Sponsor: Medical University Innsbruck
• Collaborators: Heart and Diabetes Center North Rhine-Westphalia; Austrian Science Fund (FWF)
• Investigators: Principal Investigator: Miriam Michel, MD, Medical University of Innsbruck

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2022
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: February 17, 2021
• First Submitted That Met QC Criteria: February 17, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): March 13, 2024
• Last Update Submitted That Met QC Criteria: March 11, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Fontan; inflammation; congenital heart disease; Fontan-associated liver disease; Myocardial fibrosis; Collateral vessel
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Cardiovascular Abnormalities; Liver Diseases; Fibrosis; Congenital Abnormalities; Cardiomyopathies; Heart Defects, Congenital
• Other Study ID Numbers: registration in progress

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No