Preventive Potential of Bilirubin

Completed

• Conditions: Mild Hyperbilirubinaemia
• Interventions: Other: No intervention

• Registration Number: NCT04792996
• Lead Sponsor: University of Vienna

Brief Summary

The prevalence of mild hyperbilirubinemia, also known as Gilbert´s Syndrome, is usually defined using an unconjugated bilirubin (UCB) blood concentration above 17.1 µmol/l. The prevalence of GS is remarkably common, affecting 5-10% (depending on ethnicity and gender) of the adult population.

The aim of this project is to investigate whether there is a difference in health related marker between 60 subjects with Gilbert´s Syndrome (mild hyperbilirubinaemia) and 60 age and gender matched control subjects.

Detailed Description

Not available

Study Timeline

• Study Start: 2014-06-01
• Primary Completion: 2016-06-01
• Study Completion: 2016-06-01
• Status Verified: 2021-03
• Study First Submitted: 2021-03-03
• Study First Submitted QC: 2021-03-07
• Last Update Submitted: 2021-03-07
• Study First Posted: 2021-03-11
• Last Update Posted: 2021-03-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

In general

• Signed declaration of consent
• Age: 20-80 years
• Liver enzymes (AST, ALT, GGT) < 1.5x over norm values
• Non smoking
• Moderate physical activity
• Ability to communicate with the study team in the local language to understand the study procedure

Cases (GS):

• Total blood bilirubin > 1.2 mg/dl
• Unconjugated bilirubin > 1 mg/dl

Controls (non-GS):

• Total blood bilirubin ≤ 1.2 mg/dl
• Unconjugated bilirubin ≤ 1 mg/dl

Exclusion Criteria

In general

• Age < 20 or > 80 years
• Cardiovascular diseases
• Liver diseases (including Hep B and C)
• Cholelithiasis
• Hemolysis
• Renal diseases
• Active tumors
• Diabetes mellitus
• Smoking
• Professional athletes
• Subjects with organ transplants
• Intake of antioxidants within the last 4 weeks
• Intake of liver influencing medication within the last 5 weeks

Cases (GS):

• Total blood bilirubin ≤ 1.2 mg/dl
• Unconjugated bilirubin ≤ 1 mg/dl

Controls (non-GS):

• Total blood bilirubin > 1.2 mg/dl
• Unconjugated bilirubin > 1 mg/dl

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Control group	No intervention	Healthy controls with lower plasma level of unconjugated bilirubin of 17.1 µmol, aen and gender matched.
Gilbert´s Syndrome	No intervention	Subjects with mild hyperbilirubinaemia and a plasma level of unconjugated bilirubin of 17.1 µmol.

Primary Outcome Measures

Name	Time	Method
The investigators will consider Lipid parameter	Baseline	Compare plasma parameter of lipid metabolism (Cholesterol, LDL, HDL, Triglycerides, ..) between Gilbert´s Syndrome subjects and controls.

Secondary Outcome Measures

Name	Time	Method
The investigators will consider AMPK metabolic pathway	Baseline	Compare parameter of the AMPK metabolic pathway (phosphorylated AMPK (rfU), phosphorylated Ppar-alpha (rfU), phosphorylated Ppar-gamma (rfU)) between Gilbert´s Syndrome subjects and controls.
The investigators will consider heme catabolic pathway	Baseline	Compare parameter of the heme catabolic pathway (expression of heme oxygenase (RQ), expression of Biliverdinreductase (RQ)) between Gilbert´s Syndrome subjects and controls.
The investigators will consider the metabolomic response	Baseline	Compare the metabolomic pattern (ie all metabolites; analyzed using both nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques) between Gilbert´s Syndrome subjects and controls.
The investigators will consider the composition of gut-microbiota	Baseline	Compare the composition of the gut microbiota (Gene sequencing of the 16S rRNA on the stool samples are performed to identify the microbes down to genus level as well as the microbial diversity and relative abundance) between Gilbert´s Syndrome subjects and controls.
The investigators will consider oxidative stress marker	Baseline	Compare plasma concentrations of oxidative stress marker such as malondialdehyde or GSH/GSSG between Gilbert´s Syndrome subjects and controls.
The investigators will consider telomere length	Baseline	Compare telomere length between Gilbert´s Syndrome subjects and controls.
The investigators will consider the metabolomic response after a standard breakfast	Five blood samplings over 180 minutes.	Compare the metabolomic pattern after a standard breakfast (ie all metabolites; analyzed using both nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques) between Gilbert´s Syndrome subjects and controls.
The investigators will consider plasma parameter of glucose metabolism	Baseline	Compare plasma parameter of glucose metabolism (plasma glucose (mg/dl), plasma insulin (µU/ml), C-peptide (ng/ml)) between Gilbert´s Syndrome subjects and controls.
The investigators will consider body composition	Baseline	Compare parameter of the body composition (BMI (kg/m2), fat mass (%), waist circumference (cm), hip circumference (cm), abdominal circumference (cm)) between Gilbert´s Syndrome subjects and controls.
The investigators will consider anabolic and catabolic hormones	Baseline	Compare plasma concentrations of hormones (Glucagon (pg/ml), T3 (pg/ml), TSH(µM/ml),) between Gilbert´s Syndrome subjects and controls.
The investigators will consider RNA and DNA gene expression	Baseline	Compare RNA and DNA gene expression between Gilbert´s Syndrome subjects and controls.