Non-alcoholic Fatty Liver Disease (NAFLD)ECHONCT06942312
Elucidating Hepatic Metabolism in Non-alcoholic Fatty Liver Disease
An observational study of Non-alcoholic Fatty Liver Disease (NAFLD), run by Helsinki University Central Hospital at 1 site in Finland.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Non-alcoholic Fatty Liver Disease (NAFLD)
- What is being tested?
- Ketoisocaproic acid breath test, Ammonium Chloride and Bicarbonate de sodium
- Type of treatment
- Pill or oral medicine
- How many people
- 30 participants
- Where
- 1 siteFinland
- Study dates
- 1 May 2025to 31 Dec 2030
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: General population and hospital outpatients
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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
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)?
Read the 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.
- Being tested
- Ketoisocaproic acid breath test, Ammonium Chloride, Bicarbonate de sodium, Deuterated Water, Oral Glucose Tolerance Test
- Keywords
- Hepatic mitochondrial dysfunction, Non-alcoholic Fatty Liver Disease NAFLD, 13C-α-Ketoisocaproic Acid Breath Test, liver stiffness
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketoisocaproic acid breath testDiagnostic test
13C-alpha-ketoisocaproic acid breath test to estimate hepatic mitochondrial reductive stress (1 mg/kg body weight; oral dose; study duration 390 min)
Ammonium ChlorideDiagnostic test
15N-ammonium chloride stable isotope test to estimate ureagenesis (20 mg/kg body weight; oral dose; study duration 390 min)
Bicarbonate de sodiumDiagnostic test
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)
Deuterated WaterDiagnostic test
Deuterated water stable isotope test to estimate hepatic de novo lipogenesis and gluconeogenesis (3 g/kg body water; oral dose; duration: overnight)
Oral Glucose Tolerance TestDiagnostic test
A standard 2-hour 75-gram oral glucose tolerance test to assess glucose tolerance and whole body metabolism
| Study group | Role | What they receive |
|---|---|---|
| Advanced NAFLD | Intrahepatic triglyceride content ≥ 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement ≥ 8 kPa using transient elastography (Fibroscan) Receives: Diagnostic Test: Ketoisocaproic acid breath test; Diagnostic Test: Ammonium Chloride; Diagnostic Test: Bicarbonate de sodium; Diagnostic Test: Deuterated Water; Diagnostic Test: Oral Glucose Tolerance Test | |
| Mild NAFLD | Intrahepatic triglyceride content ≥ 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement < 8 kPa using transient elastography (Fibroscan) Receives: Diagnostic Test: Ketoisocaproic acid breath test; Diagnostic Test: Ammonium Chloride; Diagnostic Test: Bicarbonate de sodium; Diagnostic Test: Deuterated Water; Diagnostic Test: Oral Glucose Tolerance Test | |
| Healthy control | Intrahepatic triglyceride content < 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement < 8 kPa using transient elastography (Fibroscan) Receives: Diagnostic Test: Ketoisocaproic acid breath test; Diagnostic Test: Ammonium Chloride; Diagnostic Test: Bicarbonate de sodium; Diagnostic Test: Deuterated Water; Diagnostic Test: Oral Glucose Tolerance Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic mitochondrial reductive stress as determined by plasma beta-hydroxybutyrate-to-acetoacetate ratio
Ratio of beta-hydroxybutyrate and acetoacetate concentrations in arterialized plasma
Measured: Fourth study visit (2 months)
Hepatic mitochondrial reductive stress as determined by the ketoisocaproic acid breath test
Breath 13CO2 enrichment after ingesting 13C-alpha-ketoisocaproate measured as area under the curve
Measured: Fourth study visit (2 months)
Secondary outcomes (2)
Plasma metabolomics
Arterialized plasma analyzed by nuclear magnetic resonance
Measured: Fourth study visit (2 months)
Plasma metabolomics
Arterialized plasma analyzed by mass spectrometry
Measured: Fourth study visit (2 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Apr 2025
- Study start1 May 2025 (estimated)
- Primary completion31 Dec 2029 (estimated)
- Study completion31 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-alcoholic Fatty Liver Disease (NAFLD)Studies of the same condition, open and under way.
- More trials run by Helsinki University Central HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Panu Luukkonen, Helsinki University Central Hospital
- Investigators
- Panu K. Luukkonen, MD, PhD, Principal investigator, University of Helsinki
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06942312
- Sponsor's protocol ID
- HUS/176/2025
- Acronym
- ECHO
- Status last verified
- Apr 2025
- First submitted
- 14 Mar 2025
- Last updated
- 24 Apr 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Due to European Union GDPR regulations.
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidating Hepatic Metabolism in Non-alcoholic Fatty Liver Disease
- ClinicalTrials.gov ID
- NCT06942312
- Acronym / sponsor ID
- ECHO / HUS/176/2025
- Keywords
- Hepatic mitochondrial dysfunction, Non-alcoholic Fatty Liver Disease NAFLD, 13C-α-Ketoisocaproic Acid Breath Test, liver stiffness
- Study type
- Observational
- Recruitment status
- Enrolling by invitation
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Study start
- 1 May 2025 (estimated)
- Primary completion
- 31 Dec 2029 (estimated)
- Study completion
- 31 Dec 2030 (estimated)
- First posted
- 24 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Advanced NAFLD | – | Diagnostic Test: Ketoisocaproic acid breath test, Diagnostic Test: Ammonium Chloride, Diagnostic Test: Bicarbonate de sodium, Diagnostic Test: Deuterated Water, Diagnostic Test: Oral Glucose Tolerance TestIntrahepatic triglyceride content ≥ 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement ≥ 8 kPa using transient elastography (Fibroscan) |
| Mild NAFLD | – | Diagnostic Test: Ketoisocaproic acid breath test, Diagnostic Test: Ammonium Chloride, Diagnostic Test: Bicarbonate de sodium, Diagnostic Test: Deuterated Water, Diagnostic Test: Oral Glucose Tolerance TestIntrahepatic triglyceride content ≥ 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement < 8 kPa using transient elastography (Fibroscan) |
| Healthy control | – | Diagnostic Test: Ketoisocaproic acid breath test, Diagnostic Test: Ammonium Chloride, Diagnostic Test: Bicarbonate de sodium, Diagnostic Test: Deuterated Water, Diagnostic Test: Oral Glucose Tolerance TestIntrahepatic triglyceride content < 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement < 8 kPa using transient elastography (Fibroscan) |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- General population and hospital outpatients
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketoisocaproic acid breath test13C-alpha-ketoisocaproic acid breath test to estimate hepatic mitochondrial reductive stress (1 mg/kg body weight; oral dose; study duration 390 min) | Diagnostic test | Advanced NAFLD, Healthy control, Mild NAFLD |
| Ammonium Chloride15N-ammonium chloride stable isotope test to estimate ureagenesis (20 mg/kg body weight; oral dose; study duration 390 min) | Diagnostic test | Advanced NAFLD, Healthy control, Mild NAFLD |
| Bicarbonate de sodium13C-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 | Advanced NAFLD, Healthy control, Mild NAFLD |
| Deuterated WaterDeuterated water stable isotope test to estimate hepatic de novo lipogenesis and gluconeogenesis (3 g/kg body water; oral dose; duration: overnight) | Diagnostic test | Advanced NAFLD, Healthy control, Mild NAFLD |
| Oral Glucose Tolerance TestA standard 2-hour 75-gram oral glucose tolerance test to assess glucose tolerance and whole body metabolism | Diagnostic test | Advanced NAFLD, Healthy control, Mild NAFLD |
Primary outcome
Hepatic mitochondrial reductive stress as determined by plasma beta-hydroxybutyrate-to-acetoacetate ratio
Time frame: Fourth study visit (2 months)
Ratio of beta-hydroxybutyrate and acetoacetate concentrations in arterialized plasma
Hepatic mitochondrial reductive stress as determined by the ketoisocaproic acid breath test
Time frame: Fourth study visit (2 months)
Breath 13CO2 enrichment after ingesting 13C-alpha-ketoisocaproate measured as area under the curve
2 secondary outcomes
Plasma metabolomics
Time frame: Fourth study visit (2 months)
Plasma metabolomics
Time frame: Fourth study visit (2 months)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2025.
- Individual participant dataSharing planned: No. Due to European Union GDPR regulations.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Panu K. Luukkonen, MD, PhD principal investigator
University of Helsinki
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Non-alcoholic Fatty Liver Disease (NAFLD), run by Helsinki University Central Hospital at 1 site in Finland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: enrolling by invitation, as of the sponsor's last update on 24 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Finland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Hepatic mitochondrial reductive stress as determined by plasma beta-hydroxybutyrate-to-acetoacetate ratio (time frame: Fourth study visit (2 months)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Apr 2025.