Enrolling by invitationNCT06559878ALPHAUpdated Aug 19, 2024

Hepatic Mitochondrial Metabolism in Fatty Liver Disease in Humans

An interventional study of 13C-α-Ketoisocaproic Acid Breath Test and Ethanol in Non-alcoholic Fatty Liver Disease NAFLD, sponsored by Helsinki University Central Hospital. Enrolling by invitation at 1 site in Finland. Open to participants aged 18 Years to 75 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-08-19.

Sponsored by Helsinki University Central Hospital · Not applicable, Interventional, and Basic science

From the registry’s dates

Primary completion was expected by Feb 2026, 7 months ago, but the record still lists the study as enrolling by invitation.

Phase: Not applicable
Study type: Interventional
Enrollment: 12
Allocation: Randomized
Ages: 18 Years to 75 Years
Sex: All

Study 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?

Read the 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 studied

Non-alcoholic Fatty Liver Disease NAFLD

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Keywords

Hepatic mitochondrial dysfunction
MAFLD
Non-alcoholic Fatty Liver Disease NAFLD
13C-α-Ketoisocaproic Acid Breath Test

In context

Liver Diseases

2,081 studies on the registry are indexed under Liver Diseases; 390 are open to participants now.

This study's planned enrollment of 12 is below the median of 50 across 1,323 interventional studies indexed under Liver Diseases.

Browse Liver Diseases studies →

Lead sponsor

Helsinki University Central Hospital is the lead sponsor of 299 studies on the registry; 60 are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 75 Years
Sexes eligible: All
Accepts healthy volunteers: Yes

Eligibility criteria

Participants must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
Subject must be likely to be available to complete all protocol-required study visits or procedures, to the best of the subject's and investigator's knowledge.
Age range from 18-75 years.
No known hypersensitivity to egg, soy, or peanut protein, or to any of the substances of Intralipid 20%, or to any other substance to be administered during the study.
No severe hyperlipidemia or hemophagocytotic syndrome as judged by history and physical examination and standard laboratory tests.
No other liver disease except for SLD.
No advanced liver disease as judged by history and physical examination and standard laboratory tests.
No claustrophobia or metal implants to allow magnetic resonance studies.
No pregnancy or lactation in women.
No known or anticipated difficulties in cannulation of peripheral veins.
No history or evidence of any other clinically significant disorder, condition or disease other than those outlined above that, in the opinion of the investigator may compromise the ability of the subject to give written informed consent, would pose a risk to subject safety, or interfere with the study evaluation, procedures or completion.
No drinking problem based on AUDIT questionnaire.
No use of medications interacting with alcohol.
No history of heparin induced thrombosytopenia (HIT) or bleeding tendency.
No current use of warfarin, direct anticoagulants, or thrombocyte inhibitors.

Study design

Phase: Not applicable
Primary purpose: Basic science
Allocation: Randomized
Intervention model: Crossover assignment
Masking: None (open label)
Enrollment: 12 participants (estimated)

Study arms

Experimental
The order of metabolic visits: 1.Normal saline, 2.Lipid emulsion, 3.Ethanol
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline
Experimental
The order of metabolic visits: 1. Normal saline, 2. Ethanol, 3. Lipid emulsion
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline
Experimental
The order of metabolic visits: 1.Lipid emulsion, 2.Normal saline, 3.Ethanol
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline
Experimental
The order of metabolic visits: 1.Lipid emulsion, 2.Ethanol, 3.Normal saline
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline
Experimental
The order of metabolic visits: 1. Ethanol, 2. Normal saline, 3. Lipid emulsion
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline
Experimental
The order of metabolic visits: 1. Ethanol, 2. Lipid emulsion, 3. Normal saline
Diagnostic Test: 13C-α-Ketoisocaproic Acid Breath Test · Dietary Supplement: Ethanol · Dietary Supplement: Lipid Emulsion · Other: Normal Saline

Interventions

Diagnostic test13C-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 supplementEthanol
6% ethanol soluted in normal saline is given intravenously during one metabolic visit.
Also known as: Alcohol
Dietary supplementLipid Emulsion
Lipid emulsion, heparin and normal saline are given intravenously during one metabolic visit.
OtherNormal Saline
Normal saline is given intravenously during one metabolic visit.

What researchers measure

Primary outcomes

Change in arterialized plasma b-OHB to AcAc ratio
Arterialized plasma b-OHB and AcAc concentrations
Time frame: From baseline to the end of treatment at 240 minutes
Breath 13CO2 enrichment after ingesting 13C-alpha-ketoisocaproate
Measured as area under the curve
Time frame: From baseline to the end of treatment at 330 minutes.

Other outcomes

Plasma metabolomics
Arterialized plasma analyzed by nuclear magnetic resonance and mass spectrometry
Time frame: From baseline until the end of treatment at 240 minutes.

Study locations

1 site

Helsinki Central University Hospital
Helsinki, Uusimaa 00290, Finland

References and documents

Individual participant data

Plan to share: No — Due to European Union GDPR regulations.

No publications or documents are linked to this record.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Aug 19, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT06559878
Lead sponsor: Helsinki University Central Hospital
Responsible party: Panu Luukkonen (MD, PhD, Helsinki University Central Hospital) — Principal investigator
First posted: Aug 19, 2024
Start date: Sep 1, 2024 (estimated)
Primary completion: Feb 28, 2026 (estimated)
Completion: Jan 31, 2027 (estimated)
Last update: Aug 19, 2024

Study contacts

Panu Luukkonen, MD, PhD

principal investigator · Helsinki University Central Hospital

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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