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

NCT06647095 | Completed

• 1 other identifier: GUHPrague83/21
• Study Type: observational
• Target: 172
• Locations: 1 country
• Sites: 2

Brief Summary

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:

• 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)

Conditions

Healthy; Simple Steatosis (SS); Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD); Metabolic Dysfunction-associated Steatohepatitis (MASH)

Keywords

Liver steatosis; Liver fibrosis; MASLD; MASH; Blood spectroscopy; Breath tests; d-Limonene; SYFT-MS; Bile acids; metabolic dysfunction-associated steatotic liver disease; metabolic dysfunction-associated steatohepatitis

Outcome Measures

Primary Outcomes (7)

• Serum bile acids concentrations in the MASH/ Steatosis/ Healthy controls

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

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

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

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

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

• Native breath concentrations of volatile organic compounds in the aim groups

  Concentrations of VOC in fasting exhaled breath expressed in ppbv

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

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

  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

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

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

  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

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

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

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

  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)

• Spectroscopic patterns of blood plasma

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

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

Study Arms (3)

Healthy controls

Dietary Supplement: D-Limonene Gelcaps; Dietary Supplement: Fish Oil Concentrate, 1000 Mg Oral Capsule

MASH

Dietary Supplement: D-Limonene Gelcaps; Dietary Supplement: Fish Oil Concentrate, 1000 Mg Oral Capsule

Steatosis

Dietary Supplement: D-Limonene Gelcaps; Dietary Supplement: Fish Oil Concentrate, 1000 Mg Oral Capsule

Interventions

D-Limonene Gelcaps DIETARY_SUPPLEMENT

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

Healthy controls; MASH; Steatosis

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

Healthy controls; MASH; Steatosis

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with MASLD of primary care clinic, healthy volunteers

You may qualify if:

• 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
• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• General University Hospital, Prague: lead

Study Sites (2)

Regional Hospital Liberec

Liberec, Czech Republic, 46001, Czechia

Location

General University Hospital in Prague

Prague, Czech Republic, 12800, Czechia

Location

Related Publications (7)

• Zizalova K, Novakova B, Vecka M, Petrtyl J, Lanska V, Pelinkova K, Smid V, Bruha R, Vitek L, Lenicek M. Serum concentration of taurochenodeoxycholic acid predicts clinically significant portal hypertension. Liver Int. 2023 Apr;43(4):888-895. doi: 10.1111/liv.15481. Epub 2022 Nov 25.

  PMID: 36433660 BACKGROUND

• WED-280 Spectroscopy of blood plasma has the potential to differentiate metabolic dysfunction-associated steatohepatitis from steatosis Nováková, Barbora et al. Journal of Hepatology, Volume 80, S539 - S540

  BACKGROUND

• Puri P, Daita K, Joyce A, Mirshahi F, Santhekadur PK, Cazanave S, Luketic VA, Siddiqui MS, Boyett S, Min HK, Kumar DP, Kohli R, Zhou H, Hylemon PB, Contos MJ, Idowu M, Sanyal AJ. The presence and severity of nonalcoholic steatohepatitis is associated with specific changes in circulating bile acids. Hepatology. 2018 Feb;67(2):534-548. doi: 10.1002/hep.29359. Epub 2017 Dec 23.

  PMID: 28696585 BACKGROUND

• Spanel P, Smith D. Quantification of volatile metabolites in exhaled breath by selected ion flow tube mass spectrometry, SIFT-MS. Clin Mass Spectrom. 2020 Feb 13;16:18-24. doi: 10.1016/j.clinms.2020.02.001. eCollection 2020 Apr.

  PMID: 34820516 BACKGROUND

• Sinha R, Lockman KA, Homer NZM, Bower E, Brinkman P, Knobel HH, Fallowfield JA, Jaap AJ, Hayes PC, Plevris JN. Volatomic analysis identifies compounds that can stratify non-alcoholic fatty liver disease. JHEP Rep. 2020 Jun 15;2(5):100137. doi: 10.1016/j.jhepr.2020.100137. eCollection 2020 Oct.

  PMID: 32775974 BACKGROUND

• Ten-Doménech I, Rienda I, Pérez-Rojas J, et al. Progress and challenges of mid-infrared spectroscopy for liver characterization focusing on steatosis, fibrosis and cancer. Applied Spectroscopy Reviews. 2024;59(4):578-599

  BACKGROUND

• Targher G, Byrne CD, Tilg H. MASLD: a systemic metabolic disorder with cardiovascular and malignant complications. Gut. 2024 Mar 7;73(4):691-702. doi: 10.1136/gutjnl-2023-330595.

  PMID: 38228377 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples, exhaled breath samples, urine samples

MeSH Terms

Conditions

Fatty Liver; Liver Cirrhosis

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Barbora Nováková, MD

  General University Hospital, Prague

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 15, 2024
• First Posted: October 17, 2024
• Study Start: September 1, 2021
• Primary Completion: September 1, 2022
• Study Completion: September 1, 2024
• Last Updated: November 1, 2024

Record last verified: 2024-10

Locations

CZ (2)