Clinical trial NCT03886935: Metabolic Remodeling in Fontan Patients
Official title: Metabolic Remodeling in Fontan Patients: a Metabolomics Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Congenital Heart Disease
Metabolism Disorder
Lead sponsor: Medical University Innsbruck
Sponsor class: OTHER
Collaborators: name: Biocrates Life Sciences AG, Innsbruck, Austria
name: Tiroler Wissenschaftsförderung
First posted: 2019-03-22
Enrollment: 100
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients ≥ 18 years with a Fontan circulation with a dominant left ventricle.

Controls: age- and sex-matched healthy biventricular controls ≥ 18 years

Brief summary: Assessment of metabolic alterations in adult Fontan patients with a dominant left ventricle with the help of serum examinations (Metabolomics). The aim is to find a tool for the completion of the (semi-)invasive monitoring of Fontan hemodynamics.

Detailed description: Patients who are born with just one single heart chamber need to undergo surgical therapy allowing the single heart chamber to pump the blood into the systemic circulation and allowing the blood to flow passively to the lungs (Fontan circulation). Regular ultrasound, cardiopulmonary exercise testing, and invasive diagnostic tools (catheterization, general anaesthesia needed) are necessary to early find out cardiac, vascular, or circulatory impairment. It is still very difficult to diagnose and therapy failure of this Fontan system early enough.

It is reported that in patients with a failing two-chambered heart, the energy source for the heart and the body in general switches from the use of lipids to the use of sugar and ketone bodies. First studies show decreased concentrations of membrane lipids in Fontan patients with a left dominant ventricle, and the energy metabolism has not been focused yet in those patients.

The investigators hypothesize that there are differences in the pattern of the structural metabolism in adult Fontan patients with a left-dominant vs. a right-dominant ventricle. Furthermore the investigators hypothesize that there are alterations in the energy metabolism in adult Fontan patients in comparison to healthy two-chambered controls, and that those alterations correlate with the grade of impairment of cardiopulmonary function.

With the help of a special biochemical examination (mass spectrometry-based Metabolomics study) blood of Fontan patients will be analyzed, and the results will be correlated with the results of ultrasound and cardiopulmonary exercise testing. The aim of this study is to establish sensitive blood markers indicating cardiac, vascular, circulatory or further organ dysfunction in Fontan patients. This should allow optimal Fontan system monitoring with an optimal timing of an additional invasive diagnostic catheterization and of nutritional, medical or interventional therapy.

Eligibility criteria: Inclusion Criteria:

* Fontan circulation (right systemic ventricle), biventricular heart with heart failure resp.
* ≥ 18 years
* Written informed consent of patients
* 8 hours fasting period before blood sample

Exclusion Criteria:

Intake of medication directly affecting metabolic (e.g. metabolism of lipids (statine)) or hemodynamic state (e.g. beta-blockers, sildenafil) (other than angiotensin converting enzyme (ACE)-inhibitors and anticoagulation therapy)

* Cachectic disease
* Non-congestive hepatic or renal dysfunction
* (Inherited) metabolic disorders

Primary outcomes:
measure: Metabolism of lipids
timeFrame: blood sampling at one single point of time (baseline/day 1) in the context of a planned patient presentation at the pediatric cardiology outpatient clinic (without assessment of changes)
measure: Metabolism of amino acids and related compounds
timeFrame: blood sampling at one single point of time (baseline/day 1) in the context of a planned patient presentation at the pediatric cardiology outpatient clinic (without assessment of changes)
measure: Metabolism of carbohydrates
timeFrame: blood sampling at one single point of time (baseline/day 1) in the context of a planned patient presentation at the pediatric cardiology outpatient clinic (without assessment of changes)
measure: Metabolism of ketone bodies
timeFrame: blood sampling at one single point of time (baseline/day 1) in the context of a planned patient presentation at the pediatric cardiology outpatient clinic (without assessment of changes)
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Medical University of Innsbruck
name: Daniela Karall, Prof.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Michel M, Salvador C, Wiedemair V, Adam MG, Laser KT, Dubowy KO, Entenmann A, Karall D, Geiger R, Zlamy M, Scholl-Burgi S. Method comparison of HPLC-ninhydrin-photometry and UHPLC-PITC-tandem mass spectrometry for serum amino acid analyses in patients with complex congenital heart disease and controls. Metabolomics. 2020 Dec 15;16(12):128. doi: 10.1007/s11306-020-01741-8.
citation: Michel M, Dubowy KO, Zlamy M, Karall D, Adam MG, Entenmann A, Keller MA, Koch J, Odri Komazec I, Geiger R, Salvador C, Niederwanger C, Muller U, Scholl-Burgi S, Laser KT. Targeted metabolomic analysis of serum phospholipid and acylcarnitine in the adult Fontan patient with a dominant left ventricle. Ther Adv Chronic Dis. 2020 Apr 27;11:2040622320916031. doi: 10.1177/2040622320916031. eCollection 2020.