Elucidating Hepatic Metabolism in Non-alcoholic Fatty Liver Disease
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: Ketoisocaproic acid breath test, Ammonium Chloride, Bicarbonate de sodium, Deuterated Water.
- Who it may be relevant to
- Registry conditions: Non-alcoholic Fatty Liver Disease (NAFLD). Basic parameters: 18 years — 75 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- Finland
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The goal of this observational, cross-sectional, case-control clinical study is to investigate the metabolic adaptations underlying the progression of nonalcoholic fatty liver disease (NAFLD), and to test the hypothesis that hepatic mitochondrial reductive stress contributes to progression of NAFLD. The main question it aims to answer is: Do patients with advanced NAFLD compared to patients with mild NAFLD and healthy controls have increased hepatic mitochondrial reductive stress as determined by the ketoisocaproate breath test and by plasma beta-hydroxybutyrate to acetoacetate ratio (b-OHB/AcAc)?
Detailed description
In this study the investigators study the metabolic adaptations underlying the progression of nonalcoholic fatty liver disease (NAFLD), namely hepatic mitochondrial reductive stress, ureagenesis, de novo lipogenesis and gluconeogenesis in patients with advanced and mild NAFLD and in healthy controls.
At the first visit, an informed consent will be obtained, followed by assessment of inclusion/exclusion criteria and medical history. Participants fulfilling the criteria will be enrolled in the study. A physical examination will be performed and laboratory test will be taken. Body composition will be determined with bioelectrical impedance and dual-energy x-ray absorptiometry (DEXA).
At the second visit, hepatic lipid content will be measured with magnetic resonance spectroscopy.
At the third visit, participants will pick up containers for overnight urine collection and doses of deuterated water and a standardized meal replacement bar. The fourth visit is a clinical study visit. In a specified order, participants will drink tracer doses of 15NH4Cl, 13C-bicarbonate and 13C-alpha-ketoisocaproate. An oral glucose tolerance test is performed in the end of the study day. Breath samples are collected at different time points for determination of 13C enrichment of CO2. Furthermore, "arterialized" blood samples are taken 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.
Interventions
- Diagnostic test Ketoisocaproic acid breath test
13C-alpha-ketoisocaproic acid breath test to estimate hepatic mitochondrial reductive stress (1 mg/kg body weight; oral dose; study duration 390 min) - Diagnostic test Ammonium Chloride
15N-ammonium chloride stable isotope test to estimate ureagenesis (20 mg/kg body weight; oral dose; study duration 390 min) - Diagnostic test Bicarbonate de sodium
13C-bicarbonate breath test to estimate body bicarbonate pool size and gastric emptying (0.5 mg/kg body weight; oral dose; study duration 390 min) - Diagnostic test Deuterated Water
Deuterated water stable isotope test to estimate hepatic de novo lipogenesis and gluconeogenesis (3 g/kg body water; oral dose; duration: overnight) - Diagnostic test Oral Glucose Tolerance Test
A standard 2-hour 75-gram oral glucose tolerance test to assess glucose tolerance and whole body metabolism
Primary outcome measures
- Hepatic mitochondrial reductive stress as determined by plasma beta-hydroxybutyrate-to-acetoacetate ratio [Time frame: Fourth study visit (2 months)]
- Hepatic mitochondrial reductive stress as determined by the ketoisocaproic acid breath test [Time frame: Fourth study visit (2 months)]
Secondary outcome measures (2)
- Plasma metabolomics [Time frame: Fourth study visit (2 months)]
- Plasma metabolomics [Time frame: Fourth study visit (2 months)]
Eligibility criteria
The following inclusion/ exclusion criteria will be employed:
- 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.
- Participants must be aged between 18-75 years.
- Participants are not allowed to have alcohol consumption of 350 g/week or more in women and 420 g/week or more in men.
- Participants are not allowed to have history of liver disease other than NAFLD as judged by history and physical examination and standard laboratory tests.
- Participants are not allowed to have claustrophobia or metal implants to allow magnetic resonance studies.
- Participants are not allowed to be pregnant or lactating.
- 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.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: Yes
Study design
- Observational model
- Case-control
Study locations
Finland · 1 center
- Helsinki Central University Hospital — Helsinki
Identifiers
NCT: NCT06942312 · HUS/176/2025