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Completed

NCT Number: NCT06647095

New Non-invasive Biomarkers of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)

The goal of this observational study is to learn if some components of blood or exhaled breath can diagnose people having more fat in their livers than is normal, because of their poorer metabolic health (for example, because of obesity and diabetes). The main questions it aims to answer are:

1. Can a method find participants with higher liver fat than healthy participants? 2. Can a method find participants in whom higher liver fat was a cause of liver inflammation or stiffness?

Participants will:

* fast overnight * have a routine blood draw * easily exhale a few times into a special device or a plastic bag and fill in a short dietary questionnaire (if participating in a breath test) * optionally swallow capsules with an orange peel extract and fish oil before exhaling, which can help get better results from breath (capsules will be medically safe and approved)

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Key information

Conditions

Healthy Digestive System Diseases Fatty Liver Fibrosis Liver Cirrhosis Liver Diseases Metabolic Dysfunction-Associated Steatohepatitis (MASH) Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Pathologic Processes Pathological Conditions, Signs and Symptoms Simple Steatosis (SS)

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Regional Hospital Liberec, Liberec, Czech Republic, Czechia

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About this study

Patients with MASLD and healthy volunteers will be offered an observational study evaluating the diagnostic role of new non-invasive experimental methods (serum bile acids, breath VOC, and plasmatic spectroscopic patterns) assessing the presence and severity of liver fibrosis and steatosis.

First, this study aims to differentiate patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) from healthy controls (or simple steatosis) using three experimental methods.

Second, the investigators aim to stratify patients with MASLD according to the presence/grade of steatosis and fibrosis (any, significant F2-3, advanced F3, cirrhosis F4) using the same methods.

Experimental methods tested in this study include:

  • analyzing the fasting spectrum of serum bile acids using liquid chromatography-mass spectrometry
  • analyzing the disease-specific spectroscopy patterns given by vibrational and chiroptical spectroscopy of blood plasma
  • analyzing trace concentrations of volatile organic compounds (VOC) in exhaled human breath using the Selected ion flow tube mass spectrometry. This contains the so-called stress test to monitor breath VOC (d-Limonene and triethylamine) after their regulated ingestion in the form of capsules

These parameters may eventually be combined with anthropometric and laboratory parameters (such as age or BMI).

Clinical examinations, blood sampling, ultrasound examinations of the liver, and liver elastography will be performed as part of routine care.

The results of the blood parameters can be retrospectively evaluated.

Approximately 60-80 participants in total were anticipated for each method. For patients who participate in breath tests, adequate insurance must be guaranteed.

Statistical processing: individual parameters will be evaluated in an exploratory and a validation group or by the PLS-DA algorithm with repeated cross-validation. A difference of p <0.05 will be considered a statistically significant change.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

for Participants with MASLD:

  • Presence of liver steatosis (detected either by hepatic ultrasonography/CAP/histologically) or MASH/simple steatosis confirmed by liver biopsy
  • Absence of secondary causes of fat accumulation in the liver and other liver disease: ruled out other etiologies of liver disease, such as viral hepatitis, drug-induced liver disease, autoimmune liver disease, biliary tract disease, and hereditary metabolic diseases

Inclusion criteria

for Negative Controls:

  • Absence of liver disease
  • For breath analysis: absence of liver steatosis (normal liver ultrasound image and CAP less than 248 dB/m)
  • For plasma spectroscopy and bile acid analysis: Body Mass Index ≤ 25 and waist-hip ratio ≤ 0.95 plus normal liver ultrasound
  • Absence of diabetes mellitus and metabolic syndrome
  • Normal liver function tests, lipid spectrum, fasting glycemia
  • Alcohol intake less than 20 g/ day (women) or 30 g/ day (men)

Exclusion criteria

  • Non-compliance with the investigation program
  • Failure to sign the informed consent form
  • Liver biopsy/clinic discrepancy
  • For LMN a TMA "stress test": fish, see fruit and citrus fruit allergy
  • Pregnancy
  • For bile acid analysis: Treatment with BA or BA sequestrants
  • For bile acid analysis: Portal hypertension (does not apply for MASH patients)
  • For bile acid analysis: Cirrhosis (does not apply for MASH patients)
  • For plasma spectroscopy: Cirrhosis
  • Anamnesis of alcohol abuse (based on GGT, carbohydrate-deficient transferrin, urinary ethyl-glucuronide, and patient's history)

Treatment and study plan

D-Limonene Gelcaps

Dietary Supplement

Capsules containing d-Limonene will be optionally given during the breath test to all participants of all groups

Fish Oil Concentrate, 1000 Mg Oral Capsule

Dietary Supplement

Capsules containing fish oil will be optionally given during the breath test to all participants of all groups

Primary outcomes

  1. Serum bile acids concentrations in the MASH/ Steatosis/ Healthy controls

    Time frame: A single day during within the data collection period = between September 2021 and September 2024

    Individual bile acid concentrations in blood serum accessed by LC-MS/MS, measured in µmol/L or expressed as detectable or undetectable

  2. The effect of serum bile acids in the MASH/ Steatosis/ Healthy controls discrimination

    Time frame: A single day during within the data collection period = between September 2021 to September 2024

    To access the effect of serum bile acid concentrations on intergroup discrimination in a discriminant model as measured by model parameters and ROC

  3. Native breath concentrations of volatile organic compounds in the aim groups

    Time frame: Single measurement on one day within 6 weeks (from mid-February 2023 to the end of March 2023)

    Concentrations of VOC in fasting exhaled breath expressed in ppbv

  4. A change in d-Limonene and TMA concentrations before and after the ingestion of capsules containing d-LMN, TMA, ppbv

    Time frame: Baseline, at 150min after capsules ingestion - both on one day within 6 weeks (from mid-February 2023 to the end of March 2023)

    A change in concentration of d-Limonene and TMA in exhaled breath after an overnight fast/ post-ingestion of d-Limonene and TMA-containing capsules, expressed in ppbv

  5. The effect of concentrations of volatile organic compounds in exhaled breath, native and post-ingestion, on the discrimination of the aim groups

    Time frame: On one day within 6 weeks (from mid-February 2023 to the end of March 2023)

    To access the effect of VOC concentrations in exhaled breath, native and after the ingestion of d-Limonene and TMA-containing capsules, on intergroup discrimination in a discriminant model as measured by model parameters and ROC

  6. Peak of d-LMN, and TMA concentration after the ingestion of capsules in the aim groups

    Time frame: At an individually specific time point for each participant that occurs within 4 hours after ingestion of d-Limonene and TMA-containing capsules on a single day within 6 weeks (from mid-February 2023 to the end of March 2023)

    A maximum concentration of d-Limonene and TMA in exhaled breath post-ingestion of d-Limonene and TMA-containing capsules, expressed in ppbv

  7. Spectroscopic patterns of blood plasma

    Time frame: Based on single peripheral blood uptake within the data collection period = between September 2021 and September 2024

    Disease-specific patterns of blood plasma expressed as differences in spectra (their normalized intensity (a.u.)) and regions between the aim groups

Sponsors and collaborators

Lead sponsor

General University Hospital, Prague

Other

Registry information

Official study title

Identification of New Non-invasive Biomarkers of Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD) in Patients by Blood Plasma Spectroscopy, Breath Volatile Organic Compounds Analysis and Serum Bile Acids Analysis

Important dates

Study start
2021
Primary completion
2022
Study completion
2024
First posted
Oct 17, 2024
Registry last updated
Nov 1, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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