Hepatic Mitochondrial Metabolism in Fatty Liver Disease in Humans
- Conditions
- Non-alcoholic Fatty Liver Disease NAFLD
- Interventions
- Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath TestDietary Supplement: EthanolDietary Supplement: Lipid EmulsionOther: Normal Saline
- Registration Number
- NCT06559878
- Lead Sponsor
- Helsinki University Central Hospital
- Brief Summary
The goal of this clinical trial is to investigate in healthy volunteers the mechanisms by which ethanol and lipids, the two key risk factors of steatotic liver disease (SLD), affect liver mitochondrial metabolism.
The main question it aims to answer is:
• Does acute administration of ethanol and lipids increase hepatic mitochondrial reductive stress as determined by orally ingested stable isotope tracer 13C-alpha-ketoisocaproate and by plasma beta-hydroxybutyrate to acetoacetate ratio (b-OHB/AcAc) in humans?
- Detailed Description
In this study we investigate the effects of ethanol and lipids on hepatic mitochondrial metabolism in healthy volunteers.
At first visit, an informed consent will be obtained, followed by assessment of inclusion/exclusion criteria. Participants fulfilling the criteria will be enrolled in the study. Body composition will be determined with bioelectrical impedance.
At second visit hepatic lipid content will be measured with magnetic resonance spectroscopy.
Participants will be given in random order on three separate visits (3-5):
* Intravenous infusion of ethanol and normal saline (breath alcohol content target and upper limit corresponding to 0.6 per mil in blood)
* Intravenous infusions of lipid emulsion, heparin and normal saline
* Intravenous infusion of normal saline
On study visits participant will drink a tracer dose of 13C-alpha-ketoisocaproate and L-Leucine. Breath samples are collected at different time points for determination of 13C enrichment of CO2. Furthermore "arterialized" blood samples are taken during study visits to obtain beta-hydroxybutyrate to acetoacetate ratios (b-OHB/AcAc) at different timepoints.
Whole-body oxidation of lipids, carbohydrates and protein will be determined using indirect calorimetry.
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 12
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description The order of metabolic visits: 1.Lipid emulsion, 2.Normal saline, 3.Ethanol 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1.Lipid emulsion, 2.Ethanol, 3.Normal saline Ethanol - The order of metabolic visits: 1. Normal saline, 2. Ethanol, 3. Lipid emulsion Normal Saline - The order of metabolic visits: 1. Ethanol, 2. Lipid emulsion, 3. Normal saline Normal Saline - The order of metabolic visits: 1. Normal saline, 2. Ethanol, 3. Lipid emulsion 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1.Normal saline, 2.Lipid emulsion, 3.Ethanol Ethanol - The order of metabolic visits: 1. Normal saline, 2. Ethanol, 3. Lipid emulsion Ethanol - The order of metabolic visits: 1.Normal saline, 2.Lipid emulsion, 3.Ethanol 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1. Ethanol, 2. Normal saline, 3. Lipid emulsion Lipid Emulsion - The order of metabolic visits: 1. Ethanol, 2. Lipid emulsion, 3. Normal saline Ethanol - The order of metabolic visits: 1.Lipid emulsion, 2.Normal saline, 3.Ethanol Normal Saline - The order of metabolic visits: 1.Lipid emulsion, 2.Ethanol, 3.Normal saline Normal Saline - The order of metabolic visits: 1. Ethanol, 2. Normal saline, 3. Lipid emulsion 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1.Lipid emulsion, 2.Normal saline, 3.Ethanol Ethanol - The order of metabolic visits: 1. Normal saline, 2. Ethanol, 3. Lipid emulsion Lipid Emulsion - The order of metabolic visits: 1.Normal saline, 2.Lipid emulsion, 3.Ethanol Lipid Emulsion - The order of metabolic visits: 1.Normal saline, 2.Lipid emulsion, 3.Ethanol Normal Saline - The order of metabolic visits: 1.Lipid emulsion, 2.Normal saline, 3.Ethanol Lipid Emulsion - The order of metabolic visits: 1.Lipid emulsion, 2.Ethanol, 3.Normal saline Lipid Emulsion - The order of metabolic visits: 1. Ethanol, 2. Normal saline, 3. Lipid emulsion Normal Saline - The order of metabolic visits: 1.Lipid emulsion, 2.Ethanol, 3.Normal saline 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1. Ethanol, 2. Normal saline, 3. Lipid emulsion Ethanol - The order of metabolic visits: 1. Ethanol, 2. Lipid emulsion, 3. Normal saline 13C-α-Ketoisocaproic Acid Breath Test - The order of metabolic visits: 1. Ethanol, 2. Lipid emulsion, 3. Normal saline Lipid Emulsion -
- Primary Outcome Measures
Name Time Method Change in arterialized plasma b-OHB to AcAc ratio From baseline to the end of treatment at 240 minutes Arterialized plasma b-OHB and AcAc concentrations
Breath 13CO2 enrichment after ingesting 13C-alpha-ketoisocaproate From baseline to the end of treatment at 330 minutes. Measured as area under the curve
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (1)
Helsinki Central University Hospital
🇫🇮Helsinki, Uusimaa, Finland