Cirrhosis, Fatty Liver
Conditions
Brief summary
Fatty liver disease is a globally widespread disease. The identification of valid biomarkers and targets for potential treatments requires in-depth knowledge about the pathophysiology of the postprandial liver. The study will consist of seven work packages (WP) including blood tests and liver biopsies taken after fasting or ingestion of a standardized meal in: healthy controls (WP 1), patients with NAFLD (WP 2), and patients with cirrhosis (WP 3) ; before and after a standardised meal in healthy controls (WP 4), and before and after glucagon in healthy controls (WP5), patients with NAFLD (WP6), and patients with T2DM and NAFLD (WP7).
Interventions
DIETARY_SUPPLEMENTStandardised meal
Standardised meal (Nutridrink, Nutricia, 300 kcal, 18.4 g carbohydrates, 5.8 g fat, 12 g protein).
DRUGGlucagon bolus
Intravenous bolus of 0.2 mg glucagon
Sponsors
Copenhagen University Hospital, Hvidovre
University of Copenhagen
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
Healthy participants (WP1 , WP4 , WP5 ): Inclusion criteria: Healthy adults, 20 - 40 years old, non-smoker, BMI 20-25 kg/m2 , no chro-nical illnesses, no medication.
Exclusion criteria
Blood donation within the past 3 months, acute illness within 2 weeks. NAFLD (WP2, WP6): Inclusion criteria: Patients with clinical diagnosis of NAFL and indication for liver biopsy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial phosphoproteomic changes in liver tissue in healthy individuals | 60 minutes after the meal administered at the study day | Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Postprandial phosphoproteomic changes in liver tissue between healthy participants and patients with cirrhosis or patients with NAFLD. | 60 minutes after the meal administered at the study day | Phosphorproteomic changes will be performed using MS-based approach that allows identification of phosphorylations sites at proteins in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in patients with cirrhosis and in patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD. |
| Postprandial proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals and compared to patients with cirrhosis and patients with NAFLD | 60 minutes after the meal administered at the study day | Proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy participants, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD. |
| Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with cirrhosis and patients with NAFLD | 120 minutes after the meal administered at the study day | Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' and 'postprandial' samples in healthy individuals, patients with cirrhosis, and patients with NAFLD and between healthy participants and patients with cirrhosis and patients with NAFLD. |
| Postprandial phosphoproteomics, proteomic, metabolomic and transcriptomic changes in liver tissue in healthy individuals. | 30 minutes after the meal administered at the study day | Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in healthy participants (paired). |
| Postprandial proteomic, metabolomic and Peptidomic changes in blood obtained from liver vein and peripheral vein in healthy individuals. | 120 minutes after the meal administered at the study day | Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted' (before) and 'postprandial' (after) samples in in healthy participants (paired). |
| Effect of exogenous glucagon on changes in liver phosphoproteomics, proteomics, metabolomics, and transcriptomics in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD. | 30 minutes after the glucagon administered at the study day | Phosphoproteomic, proteomic, metabolomic and transcriptomic changes will be performed using MS-based approaches and Next generation sequencing that allows identification of proteins, metabolites, RNA-transcripts in the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD. |
| Effect of exogenous glucagon on changes in phosphoproteomics, proteomics, metabolomics and peptidomic in blood obtained from liver vein and peripheral vein in healthy individuals and compared to patients with NAFLD and patients with T2DM and NAFLD | 120 minutes after the glucagon administered at the study day | Proteomic, metabolomic and hormonal changes will be performed using MS-based approaches and ELISAs that allows identification and measurements of proteins, metabolites and hormones from the liver. The comparison will be done between 'fasted'/baseline samples and samples obtained after glucagon injection (paired) in healthy individuals, in patients with NAFLD, and in patients with T2DM and NAFLD and between healthy participants and patients with NAFLD and patients with T2DM and NAFLD. |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORNicolai Jacob Wewer Albrechtsen, MD, Assoc. Prof.
NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark
PRINCIPAL_INVESTIGATORLise Lotte Gluud, MD, Prof
Gastrounit, Copenhagen University Hospital Hvidovre, Denmark
Outcome results
None listed