NCT06942312

Brief 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. 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)?

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for all trials

Timeline
57mo left

Started May 2025

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
enrolling by invitation

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress18%
May 2025Dec 2030

First Submitted

Initial submission to the registry

March 14, 2025

Completed
1 month until next milestone

First Posted

Study publicly available on registry

April 24, 2025

Completed
7 days until next milestone

Study Start

First participant enrolled

May 1, 2025

Completed
4.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2029

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2030

Last Updated

April 24, 2025

Status Verified

April 1, 2025

Enrollment Period

4.7 years

First QC Date

March 14, 2025

Last Update Submit

April 16, 2025

Conditions

Non-alcoholic Fatty Liver Disease (NAFLD)

Keywords

Hepatic mitochondrial dysfunctionNon-alcoholic Fatty Liver Disease NAFLD13C-α-Ketoisocaproic Acid Breath Testliver stiffness

Outcome Measures

Primary Outcomes (2)

  • Hepatic mitochondrial reductive stress as determined by plasma beta-hydroxybutyrate-to-acetoacetate ratio

    Ratio of beta-hydroxybutyrate and acetoacetate concentrations in arterialized plasma

    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

    Fourth study visit (2 months)

Secondary Outcomes (2)

  • Plasma metabolomics

    Fourth study visit (2 months)

  • Plasma metabolomics

    Fourth study visit (2 months)

Other Outcomes (5)

  • Fractional Rate of Ureagenesis

    Fourth study visit (2 months)

  • Fractional Rate of Hepatic de novo lipogenesis

    Fourth study visit (2 months)

  • Fractional Rate of Gluconeogenesis

    Fourth study visit (2 months)

  • +2 more other outcomes

Study Arms (3)

Advanced NAFLD

Intrahepatic triglyceride content ≥ 5.56 % as determined by magnetic resonance specroscopy and liver stiffness measurement ≥ 8 kPa using transient elastography (Fibroscan)

Diagnostic Test: Ketoisocaproic acid breath testDiagnostic Test: Ammonium ChlorideDiagnostic Test: Bicarbonate de sodiumDiagnostic Test: Deuterated WaterDiagnostic 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)

Diagnostic Test: Ketoisocaproic acid breath testDiagnostic Test: Ammonium ChlorideDiagnostic Test: Bicarbonate de sodiumDiagnostic Test: Deuterated WaterDiagnostic 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)

Diagnostic Test: Ketoisocaproic acid breath testDiagnostic Test: Ammonium ChlorideDiagnostic Test: Bicarbonate de sodiumDiagnostic Test: Deuterated WaterDiagnostic Test: Oral Glucose Tolerance Test

Interventions

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)

Advanced NAFLDHealthy controlMild NAFLD
Ammonium ChlorideDIAGNOSTIC_TEST

15N-ammonium chloride stable isotope test to estimate ureagenesis (20 mg/kg body weight; oral dose; study duration 390 min)

Advanced NAFLDHealthy controlMild NAFLD
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)

Advanced NAFLDHealthy controlMild NAFLD
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)

Advanced NAFLDHealthy controlMild NAFLD
Oral Glucose Tolerance TestDIAGNOSTIC_TEST

A standard 2-hour 75-gram oral glucose tolerance test to assess glucose tolerance and whole body metabolism

Advanced NAFLDHealthy controlMild NAFLD

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

General population and hospital outpatients

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Helsinki Central University Hospital

Helsinki, Uusimaa, Finland

Location

Biospecimen

Retention: SAMPLES WITH DNA

Plasma, serum, whole blood, breath samples, urine

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Glucose Tolerance Test

Condition Hierarchy (Ancestors)

Fatty LiverLiver DiseasesDigestive System Diseases

Intervention Hierarchy (Ancestors)

Blood Chemical AnalysisClinical Chemistry TestsClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisDiagnostic Techniques, EndocrineInvestigative Techniques

Study Officials

  • Panu K. Luukkonen, MD, PhD

    University of Helsinki

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
CASE CONTROL
Time Perspective
CROSS SECTIONAL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

March 14, 2025

First Posted

April 24, 2025

Study Start

May 1, 2025

Primary Completion (Estimated)

December 31, 2029

Study Completion (Estimated)

December 31, 2030

Last Updated

April 24, 2025

Record last verified: 2025-04

Data Sharing

IPD Sharing
Will not share

Due to European Union GDPR regulations.

Locations

FI(1)