Ignite Creation Date:
2024-05-06 @ 8:18 PM
Last Modification Date:
2024-10-26 @ 3:25 PM
Study NCT ID:
NCT06336369
Status:
RECRUITING
Last Update Posted:
2024-03-28
First Post:
2024-03-21
Brief Title:
Brown Adipose Tissue Activity in Gilberts Syndrome
Sponsor:
Medical University of Vienna
Organization:
Medical University of Vienna
Study Overview
Official Title:
BiliMetHealth- Energy Metabolism and Brown Adipose Tissue BAT Activity in Individuals With Gilberts Syndrome GS and Healthy Controls
Status:
RECRUITING
Status Verified Date:
2024-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The goal of this case-control study is to investigate energy metabolism and brown adipose tissue BAT activity in individuals with Gilberts syndrome GS and controls The main focus of the study is to analyze
1 the link between bilirubin metabolism and metabolic health
2 energy metabolism and body composition in individuals with Gilberts syndrome and control subjects
3 brown adipose tissue activity in Gilberts syndrome and healthy controls
Participants will undergo the following investigations
1 cold exposure
2 PET-CT imaging with 18-F-FDG
3 MRI imaging of liver abdominal fat and muscle
4 blood sampling
5 indirect calorimetry
6 bioelectrical impedance analysis
7 infrared thermography
Researchers will compare individuals with GS and control subjects in terms of metabolic health body composition and BAT activity
1 the link between bilirubin metabolism and metabolic health
2 energy metabolism and body composition in individuals with Gilberts syndrome and control subjects
3 brown adipose tissue activity in Gilberts syndrome and healthy controls
Participants will undergo the following investigations
1 cold exposure
2 PET-CT imaging with 18-F-FDG
3 MRI imaging of liver abdominal fat and muscle
4 blood sampling
5 indirect calorimetry
6 bioelectrical impedance analysis
7 infrared thermography
Researchers will compare individuals with GS and control subjects in terms of metabolic health body composition and BAT activity
Detailed Description:
Bilirubin has long been associated with liver pathology and haemolytic conditions and was until recently assumed to possess little or no biological function However unconjugated bilirubin UCB rarely approaches these toxic levels and approximates 10 μM in the general population which is 30-60 times below the reported toxic threshold
The beneficial associations of mildly elevated blood UCB concentrations with diseases of civilization in particular those affecting the cardiovascular system and all-cause mortality have been reported in numerous studies In addition a mildly elevated UCB is also associated with reduced adiposity decreased risk of metabolic syndrome non-alcoholic fatty liver disease and diabetes as well as overall cancer risk Bilirubin downregulates pro-inflammatory responses often observed in disease which complements epidemiological evidence of reduced inflammatory autoimmune and degenerative diseases in individuals with GS Together these observations may account for the reduced all-cause mortality rates reported in those with GS compared to the normobilirubinaemic population Finally bilirubin has been recently reported to modulate cell signalling and act as an endocrine molecule We were amongst the first to show that - bile pigments possess substantial anti-mutagenic in vitro and ex vivo antioxidant capacity - subjects with mild hyperbilirubinaemia - also called Gilbert s Syndrome GS have a significantly reduced BMI compared to age and gender matched controls a lower hip circumference HC as well as lower totalLDL cholesterol triglycerides and low- and pro-atherogenic sub fractions as well as IL-6 Interestingly effects of GS in older participants 35yrs is most profound with substantially reduced anthropometric data and improved lipid profile
Very recently we and others showed that enhanced lipid catabolism in GS seems to be the key mechanism involved
Based on these very preliminary observations and the strong link between bilirubin metabolism and metabolic health we aim to investigate in this application more deeply mechanistic questions to better understand why GS subjects show the very specific phenotype and its metabolic potential
Here we propose a human case control study Therefore we will investigate 40 GS individuals vs 40 age and gender matched controls Participants will be recruited as performed in previous studies
Cases Gilbert-Syndrom
Total bilirubin in the blood 12 mgdL 171 μM
Unconjugated indirect bilirubin 1 mgdL
Controls non-Gilbert-Syndrom
Total bilirubin in the blood 12 mgdL 171 μM
Unconjugated indirect bilirubin 1 mgdL
The duration of the study lasts for every participant 3 independent days On the preinvestigation-day a screening will be performed including a blood sampling to prove in- and exclusion criteria
On study day 1 participants must be fastened and will undergo the measurement of the brown adipose tissue
On study day 2 participants must be fastened and will undergo the measurement of fat distribution in liver and muscle
One 24-hr recall a FFQ and a physical activity questionnaire will be assessed at the beginning of study day 1
The beneficial associations of mildly elevated blood UCB concentrations with diseases of civilization in particular those affecting the cardiovascular system and all-cause mortality have been reported in numerous studies In addition a mildly elevated UCB is also associated with reduced adiposity decreased risk of metabolic syndrome non-alcoholic fatty liver disease and diabetes as well as overall cancer risk Bilirubin downregulates pro-inflammatory responses often observed in disease which complements epidemiological evidence of reduced inflammatory autoimmune and degenerative diseases in individuals with GS Together these observations may account for the reduced all-cause mortality rates reported in those with GS compared to the normobilirubinaemic population Finally bilirubin has been recently reported to modulate cell signalling and act as an endocrine molecule We were amongst the first to show that - bile pigments possess substantial anti-mutagenic in vitro and ex vivo antioxidant capacity - subjects with mild hyperbilirubinaemia - also called Gilbert s Syndrome GS have a significantly reduced BMI compared to age and gender matched controls a lower hip circumference HC as well as lower totalLDL cholesterol triglycerides and low- and pro-atherogenic sub fractions as well as IL-6 Interestingly effects of GS in older participants 35yrs is most profound with substantially reduced anthropometric data and improved lipid profile
Very recently we and others showed that enhanced lipid catabolism in GS seems to be the key mechanism involved
Based on these very preliminary observations and the strong link between bilirubin metabolism and metabolic health we aim to investigate in this application more deeply mechanistic questions to better understand why GS subjects show the very specific phenotype and its metabolic potential
Here we propose a human case control study Therefore we will investigate 40 GS individuals vs 40 age and gender matched controls Participants will be recruited as performed in previous studies
Cases Gilbert-Syndrom
Total bilirubin in the blood 12 mgdL 171 μM
Unconjugated indirect bilirubin 1 mgdL
Controls non-Gilbert-Syndrom
Total bilirubin in the blood 12 mgdL 171 μM
Unconjugated indirect bilirubin 1 mgdL
The duration of the study lasts for every participant 3 independent days On the preinvestigation-day a screening will be performed including a blood sampling to prove in- and exclusion criteria
On study day 1 participants must be fastened and will undergo the measurement of the brown adipose tissue
On study day 2 participants must be fastened and will undergo the measurement of fat distribution in liver and muscle
One 24-hr recall a FFQ and a physical activity questionnaire will be assessed at the beginning of study day 1
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None