Brown Adipose Tissue Activity in Gilbert's Syndrome

NCT06336369 | Recruiting

• 1 other identifier: 1713/2023
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this case-control study is to investigate energy metabolism and brown adipose tissue (BAT) activity in individuals with Gilbert's syndrome (GS) and controls. The main focus of the study is to analyze:

1. 1.the link between bilirubin metabolism and metabolic health.
2. 2.energy metabolism and body composition in individuals with Gilbert's syndrome and control subjects
3. 3.brown adipose tissue activity in Gilbert's syndrome and healthy controls.
4. 4.cold exposure
5. 5.PET-CT imaging with 18-F-FDG
6. 6.MRI imaging of liver, abdominal fat and muscle
7. 7.blood sampling
8. 8.indirect calorimetry
9. 9.bioelectrical impedance analysis
10. 10.infrared thermography

Conditions

Gilbert Syndrome

Outcome Measures

Primary Outcomes (1)

• cold-induced brown adipose tissue (BAT) activation

  proven via PET-CT imaging due to radioactive tracer uptake (18-F-FDG)

  3 independent days, 12 hours in total

Study Arms (2)

Cases

Cases: (Gilbert-Syndrom): * Total bilirubin in the blood \> 1.2 mg/dL (17.1 μM) * Unconjugated (indirect bilirubin) \> 1 mg/dL

Diagnostic Test: analyzing brown adipose tissue, body composition and metabolic health

Controls

Controls (non-Gilbert-Syndrom): * Total bilirubin in the blood ≤ 1.2 mg/dL (17.1 μM) * Unconjugated (indirect bilirubin) ≤ 1 mg/dL

Diagnostic Test: analyzing brown adipose tissue, body composition and metabolic health

Interventions

analyzing brown adipose tissue, body composition and metabolic health DIAGNOSTIC_TEST

cooling procedure, PET-CT imaging, MR imaging, blood sampling, indirect calorimetry, thermograpy, impedance analysis

Cases; Controls

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

cohort from previous study

You may qualify if:

• written consent, age between 18 and 65 years of age, liver marker (AST, ALT, GGT) \< 2x of the upper norm range, non-smoker, moderate physical activity, ability to understand the requirements of the course of study
• Cases: (Gilbert-Syndrom):
• Total bilirubin in the blood \> 1.2 mg/dL (17.1 μM)
• Unconjugated (indirect bilirubin) \> 1 mg/dL
• Controls (non-Gilbert-Syndrom):
• Total bilirubin in the blood ≤ 1.2 mg/dL (17.1 μM)
• Unconjugated (indirect bilirubin) ≤ 1 mg/dL

You may not qualify if:

• age \< 18 or \> 65 years; having current or any history of cardio-pulmonary, metabolic or musculoskeletal disease; breastfeeding or was/potentially pregnant; liver diseases incl. hep A and B; kidney diseases; active tumor disease; persons with an organ transplant; not willing to meet the demands of the study; not being weight stable (± 5% body mass; self-reported) for at least the 3 months prior to their involvement; or any conditions or concurrent behaviour (including medication) that may have posed undue personal risk to the participant, introduce bias to the study or were influencing liver marker in the last 5 weeks.
• Cases: (Gilbert-Syndrom):
• Total bilirubin in the blood ≤ 1.2 mg/dL (17.1 μM)
• Unconjugated (indirect bilirubin) ≤ 1 mg/dL
• Controls (non-Gilbert-Syndrom):
• Total bilirubin in the blood \> 1.2 mg/dL (17.1 μM)
• Unconjugated (indirect bilirubin) \> 1 mg/dL

Sponsors & Collaborators

• Medical University of Vienna: lead
• University of Vienna: collaborator
• Griffith University: collaborator

Study Sites (1)

Medical University of Vienna

Vienna, 1090, Austria

RECRUITING

Related Publications (18)

• Bulmer AC, Blanchfield JT, Toth I, Fassett RG, Coombes JS. Improved resistance to serum oxidation in Gilbert's syndrome: a mechanism for cardiovascular protection. Atherosclerosis. 2008 Aug;199(2):390-6. doi: 10.1016/j.atherosclerosis.2007.11.022. Epub 2007 Dec 26.

  PMID: 18155709 BACKGROUND

• Wagner KH, Wallner M, Molzer C, Gazzin S, Bulmer AC, Tiribelli C, Vitek L. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clin Sci (Lond). 2015 Jul;129(1):1-25. doi: 10.1042/CS20140566.

  PMID: 25881719 BACKGROUND

• Wagner KH, Shiels RG, Lang CA, Seyed Khoei N, Bulmer AC. Diagnostic criteria and contributors to Gilbert's syndrome. Crit Rev Clin Lab Sci. 2018 Mar;55(2):129-139. doi: 10.1080/10408363.2018.1428526. Epub 2018 Feb 1.

  PMID: 29390925 BACKGROUND

• Vitek L. The role of bilirubin in diabetes, metabolic syndrome, and cardiovascular diseases. Front Pharmacol. 2012 Apr 3;3:55. doi: 10.3389/fphar.2012.00055. eCollection 2012.

  PMID: 22493581 BACKGROUND

• Vitek L. Bilirubin and atherosclerotic diseases. Physiol Res. 2017 Apr 5;66(Suppl 1):S11-S20. doi: 10.33549/physiolres.933581.

  PMID: 28379026 BACKGROUND

• Weaver L, Hamoud AR, Stec DE, Hinds TD Jr. Biliverdin reductase and bilirubin in hepatic disease. Am J Physiol Gastrointest Liver Physiol. 2018 Jun 1;314(6):G668-G676. doi: 10.1152/ajpgi.00026.2018. Epub 2018 Mar 1.

  PMID: 29494209 BACKGROUND

• Jangi S, Otterbein L, Robson S. The molecular basis for the immunomodulatory activities of unconjugated bilirubin. Int J Biochem Cell Biol. 2013 Dec;45(12):2843-51. doi: 10.1016/j.biocel.2013.09.014. Epub 2013 Oct 19.

  PMID: 24144577 BACKGROUND

• Horsfall LJ, Nazareth I, Pereira SP, Petersen I. Gilbert's syndrome and the risk of death: a population-based cohort study. J Gastroenterol Hepatol. 2013 Oct;28(10):1643-7. doi: 10.1111/jgh.12279.

  PMID: 23701650 BACKGROUND

• Vitek L, Haluzik M. The role of bile acids in metabolic regulation. J Endocrinol. 2016 Mar;228(3):R85-96. doi: 10.1530/JOE-15-0469. Epub 2016 Jan 5.

  PMID: 26733603 BACKGROUND

• Bulmer AC, Ried K, Blanchfield JT, Wagner KH. The anti-mutagenic properties of bile pigments. Mutat Res. 2008 Jan-Feb;658(1-2):28-41. doi: 10.1016/j.mrrev.2007.05.001. Epub 2007 May 18.

  PMID: 17602853 BACKGROUND

• Bulmer AC, Ried K, Coombes JS, Blanchfield JT, Toth I, Wagner KH. The anti-mutagenic and antioxidant effects of bile pigments in the Ames Salmonella test. Mutat Res. 2007 May 18;629(2):122-32. doi: 10.1016/j.mrgentox.2007.01.008. Epub 2007 Feb 11.

  PMID: 17350329 BACKGROUND

• Wallner M, Blassnigg SM, Marisch K, Pappenheim MT, Mullner E, Molzer C, Nersesyan A, Marculescu R, Doberer D, Knasmuller S, Bulmer AC, Wagner KH. Effects of unconjugated bilirubin on chromosomal damage in individuals with Gilbert's syndrome measured with the micronucleus cytome assay. Mutagenesis. 2012 Nov;27(6):731-5. doi: 10.1093/mutage/ges039. Epub 2012 Aug 8.

  PMID: 22874647 BACKGROUND

• Wallner M, Antl N, Rittmannsberger B, Schreidl S, Najafi K, Mullner E, Molzer C, Ferk F, Knasmuller S, Marculescu R, Doberer D, Poulsen HE, Vitek L, Bulmer AC, Wagner KH. Anti-genotoxic potential of bilirubin in vivo: damage to DNA in hyperbilirubinemic human and animal models. Cancer Prev Res (Phila). 2013 Oct;6(10):1056-63. doi: 10.1158/1940-6207.CAPR-13-0125. Epub 2013 Aug 27.

  PMID: 23983086 BACKGROUND

• Seyed Khoei N, Grindel A, Wallner M, Molzer C, Doberer D, Marculescu R, Bulmer A, Wagner KH. Mild hyperbilirubinaemia as an endogenous mitigator of overweight and obesity: Implications for improved metabolic health. Atherosclerosis. 2018 Feb;269:306-311. doi: 10.1016/j.atherosclerosis.2017.12.021. Epub 2017 Dec 14.

  PMID: 29279144 BACKGROUND

• Wallner M, Marculescu R, Doberer D, Wolzt M, Wagner O, Vitek L, Bulmer AC, Wagner KH. Protection from age-related increase in lipid biomarkers and inflammation contributes to cardiovascular protection in Gilbert's syndrome. Clin Sci (Lond). 2013 Sep;125(5):257-64. doi: 10.1042/CS20120661.

  PMID: 23566065 BACKGROUND

• Molzer C, Wallner M, Kern C, Tosevska A, Schwarz U, Zadnikar R, Doberer D, Marculescu R, Wagner KH. Features of an altered AMPK metabolic pathway in Gilbert's Syndrome, and its role in metabolic health. Sci Rep. 2016 Jul 21;6:30051. doi: 10.1038/srep30051.

  PMID: 27444220 BACKGROUND

• Stec DE, John K, Trabbic CJ, Luniwal A, Hankins MW, Baum J, Hinds TD Jr. Bilirubin Binding to PPARalpha Inhibits Lipid Accumulation. PLoS One. 2016 Apr 12;11(4):e0153427. doi: 10.1371/journal.pone.0153427. eCollection 2016.

  PMID: 27071062 BACKGROUND

• Hana CA, Tran LV, Molzer C, Mullner E, Hormann-Wallner M, Franzke B, Tosevska A, Zohrer PA, Doberer D, Marculescu R, Bulmer AC, Freisling H, Moazzami AA, Wagner KH. Serum metabolomics analysis reveals increased lipid catabolism in mildly hyperbilirubinemic Gilbert's syndrome individuals. Metabolism. 2021 Dec;125:154913. doi: 10.1016/j.metabol.2021.154913. Epub 2021 Oct 20.

  PMID: 34653509 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood samples

MeSH Terms

Conditions

Gilbert Disease

Interventions

Body Composition

Condition Hierarchy (Ancestors)

Hyperbilirubinemia, Hereditary; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Biochemical Phenomena; Chemical Phenomena; Metabolism; Body Constitution; Physiological Phenomena

Study Officials

• Karl-Heinz Wagner, Univ.-Prof. Mag.

  University of Vienna

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karl-Heinz Wagner, Univ.-Prof. Mag.

CONTACT

+43-1- 4277 - 54930; karl-heinz.wagner@univie.ac.at

Florian Kiefer, MD, PhD

CONTACT

+43-140400-72690; florian.kiefer@meduniwien.ac.at

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Florian Kiefer MD, PhD

Study Record Dates

• First Submitted: March 21, 2024
• First Posted: March 28, 2024
• Study Start: March 6, 2024
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027
• Last Updated: March 28, 2024

Record last verified: 2024-03

Locations

AU (1)