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

Sponsor

Medical University Innsbruck (Other)

Overall Status

Recruiting

CT.gov ID

NCT04764305

Collaborator

Heart and Diabetes Center North Rhine-Westphalia (Other), Austrian Science Fund (FWF) (Other)

300

Enrollment

Location

Anticipated Duration (Months)

14.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Patient Participation Heart Defects, Congenital Liver Diseases Collateral Circulation, Any Site Myocardial Fibrosis

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 Design

Study Type:

Observational

Anticipated Enrollment :

300 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

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

Actual Study Start Date :

Apr 1, 2022

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Patients Patients with Fontan circulation. No intervention planned (observational study)
Controls Healthy, biventricular controls. No intervention planned (observational study)

Outcome Measures

Primary Outcome Measures

Number of participants [July 2021-December 2023]
When aspired number of participants is reached

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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