NCT06559878

Hepatic Mitochondrial Metabolism in Fatty Liver Disease in Humans

• Status: Enrolling By Invitation
• Phase: N/A
• Study type: Interventional
• Enrollment: 12 (estimated)
• Sponsor: Helsinki University Central Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Accepted

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.

Conditions

• Non-alcoholic Fatty Liver Disease NAFLD

Interventions

Type	Name	Description
DIAGNOSTIC_TEST	13C-α-Ketoisocaproic Acid Breath Test	13C-α-Ketoisocaproic acid with L-Leucine soluted in citric acid drink. The solution is administered orally during metabolic visits (3.-5.).
DIETARY_SUPPLEMENT	Ethanol	6% ethanol soluted in normal saline is given intravenously during one metabolic visit.
DIETARY_SUPPLEMENT	Lipid Emulsion	Lipid emulsion, heparin and normal saline are given intravenously during one metabolic visit.
OTHER	Normal Saline	Normal saline is given intravenously during one metabolic visit.

Timeline

• Start date: 2024-09-01
• Primary completion: 2026-02-28
• Completion: 2027-01-31
• First posted: 2024-08-19
• Last updated: 2024-08-19

Locations

1 site across 1 country: Finland