Preventive Potential of Bilirubin (BILIHEALTH)

Investigating the Preventive Potential of Bilirubin

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.

Study Overview

• Status: Completed
• Conditions: Mild Hyperbilirubinaemia
• Intervention / Treatment: Other: No intervention

• Study Type: Observational
• Enrollment (Actual): 120

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

120 participants, 60 participants with mild hyperbilirubinaemia, 60 subjects without mild hyperbilirubinaemia, age and gender matching.

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Gilbert´s Syndrome; Subjects with mild hyperbilirubinaemia and a plasma level of unconjugated bilirubin of 17.1 µmol.	Other: No intervention; No intervention. case - control design.
Control group; Healthy controls with lower plasma level of unconjugated bilirubin of 17.1 µmol, aen and gender matched.	Other: No intervention; No intervention. case - control design.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The investigators will consider plasma parameter of glucose metabolism	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.	Baseline
The investigators will consider AMPK metabolic pathway	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.	Baseline
The investigators will consider body composition	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.	Baseline
The investigators will consider heme catabolic pathway	Compare parameter of the heme catabolic pathway (expression of heme oxygenase (RQ), expression of Biliverdinreductase (RQ)) between Gilbert´s Syndrome subjects and controls.	Baseline
The investigators will consider the metabolomic response	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.	Baseline
The investigators will consider the composition of gut-microbiota	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.	Baseline
The investigators will consider oxidative stress marker	Compare plasma concentrations of oxidative stress marker such as malondialdehyde or GSH/GSSG between Gilbert´s Syndrome subjects and controls.	Baseline
The investigators will consider anabolic and catabolic hormones	Compare plasma concentrations of hormones (Glucagon (pg/ml), T3 (pg/ml), TSH(µM/ml),) between Gilbert´s Syndrome subjects and controls.	Baseline
The investigators will consider telomere length	Compare telomere length between Gilbert´s Syndrome subjects and controls.	Baseline
The investigators will consider RNA and DNA gene expression	Compare RNA and DNA gene expression between Gilbert´s Syndrome subjects and controls.	Baseline
The investigators will consider the metabolomic response after a standard breakfast	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.	Five blood samplings over 180 minutes.

Collaborators and Investigators

• Sponsor: University of Vienna
• Collaborators: Medical University of Vienna

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2014
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: March 3, 2021
• First Submitted That Met QC Criteria: March 7, 2021
• First Posted (Actual): March 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: March 7, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Hyperbilirubinemia
• Other Study ID Numbers: UNIVIE-BILIHEALTH

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