Assessment of Gut Microbiota-Derived Amino Acid Metabolite Production in Patients With MASLD (MASLD-GUT)

April 2, 2026 updated by: Hospices Civils de Lyon

Evaluation of the Production of Amino Acid-Derived Metabolites by the Gut Microbiota of Patients With Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver disorders ranging from simple steatosis-a relatively benign and non-progressive condition-to metabolic dysfunction-associated steatohepatitis (MASH), characterized by hepatocellular inflammation. MASLD is now the leading cause of chronic liver disease worldwide, affecting approximately one in three adults, particularly those with obesity or type 2 diabetes.

Recent studies have highlighted a strong interconnection between the gut microbiota, the liver, metabolism, and the immune system, collectively referred to as the gut-liver axis. Alterations in the gut microbiota are observed at all stages of MASLD, and several microbial metabolites-such as trimethylamine, bile acids, short-chain fatty acids, and ethanol-have been implicated in disease progression.

Emerging evidence points to a role for gut-derived metabolites of tryptophan (Trp) and phenylalanine (Phe), including phenylacetic acid (PAA), 3-(4-hydroxyphenyl)-lactate (HPL), and phenyllactate (PL). These compounds have been associated with the severity of MASLD, particularly with hepatic steatosis and fibrosis. Elevated plasma levels of aromatic amino acids (AAAs), such as L-phenylalanine and L-tyrosine, are also correlated with increased hepatic fat content.

A newly identified Phe-derived metabolite, N-acetyl-phenylalanine (NAPA), together with PAA, HPL, and PL, has been shown to correlate with hepatic steatosis. These metabolites can induce steatosis both in vitro and in vivo, acting through the disruption of endoplasmic reticulum-mitochondria interactions. They therefore represent potential new therapeutic targets.

These four metabolites of interest (NAPA, PAA, HPL, PL) can be produced both by gut bacteria and through endogenous human metabolism. Positive correlations between plasma NAPA concentrations and specific bacterial species have been observed, although the responsible taxa remain to be identified.

HYPOTHESIS

We hypothesize that the gut microbiota of MASLD patients produces aromatic amino acid-derived metabolites, contributing to the elevated plasma concentrations observed in these patients

Two complementary strategies will be used : Human Microbiota Culture and Fecal Microbiota Transplantation

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

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Intervention / Treatment

Intervention / Treatment

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Study Type

Study Type

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Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
24

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

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Study Contact

Study Contact

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Study Contact Backup

Study Locations

  • France
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier Lyon Sud Service Endocrinologie, Diabète et nutrition
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • For patients and healthy volunteers:

    • Age between 18 and 80 years.
    • Non-diabetic participant (fasting blood glucose < 1.26 g/L, or absence of insulin therapy or oral antidiabetic medication).
    • Body mass index (BMI) between 18 and 30 kg/m².
    • For women of childbearing potential, use of at least one recognized effective contraceptive method.
    • Very regular bowel movements every 24 to 48 hours.
    • Participant living within 100 km of the Lyon Sud Hospital Center (CHLS).
    • Participant willing to participate in the study and providing written informed consent.
    • Participant affiliated with the general French Social Security system or an equivalent scheme.

  • For patients:

    • Presence of MASLD according to the definition of the European Association for the Study of the Liver (EASL), defined by hepatic steatosis on imaging performed within the previous year (abdominal ultrasound, abdominal CT scan, magnetic resonance imaging, or controlled attenuation parameter (CAP) measured by FibroScan) and at least one cardiometabolic criterion among: dyslipidemia, arterial hypertension, overweight (BMI ≥ 25 kg/m²), impaired glucose tolerance, or type 2 diabetes.
    • No history of liver transplantation.
    • No excessive alcohol consumption (less than 20 g/day for women and less than 30 g/day for men).
    • Patient followed in the Endocrinology, Diabetes and Nutrition Department at Lyon Sud Hospital.

Exclusion Criteria:

  • For patients and healthy volunteers:

    • Participant with active inflammatory, infectious, cardiovascular, or neoplastic disease.
    • Participant with a history of colectomy, small bowel resection, or cholecystectomy.
    • Participant who received antibiotics, prebiotics, or probiotics within the past 3 months.
    • Participant using laxatives (more than 2 doses per day over the past 3 months).
    • Participant with chronic constipation.
    • Pregnant, parturient, or breastfeeding women.
    • Participant deprived of liberty by judicial or administrative decision.
    • Participant receiving psychiatric care.
    • Participant institutionalized for reasons other than research.
    • Adult participant under legal protection (guardianship or trusteeship).
    • Participant who does not understand the French language and cannot provide informed consent.
    • Participant already enrolled in a study presenting a conflict of interest with the present study.

  • For healthy volunteers

    • Known liver disease
    • No long-term drug medication except oral contraception for women.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: MASLD Group
Patients with metabolic dysfunction-associated steatotic liver disease Participants in this group are adults (18-80 years) with confirmed MASLD based on recent imaging and at least one associated cardiometabolic risk factor. These patients are already monitored in the Endocrinology, Diabetes, and Nutrition Department at Lyon Sud Hospital.
Procedure: stool sampling, dietary assessment, and collection of blood and urine samples

MASLD group includes individuals receiving routine clinical care for liver-related conditions. During their scheduled medical visits, participants undergo standard clinical assessments and routine blood tests. Additional research-specific procedures-such as stool sampling, dietary assessment, and collection of blood and urine samples-are carried out without altering routine patient management. A fraction of blood sample is used for NAPA measurement. Stool samples are collected at home and returned directly to the Endocrinology, Diabetes and Nutrition Department within 24 hours after collection.

Healthy volunteers undergo the same research-specific procedures as patients but exclusively for research purposes, with no routine-care-related assessments.
Other: Healthy Volunteers Group

Healthy volunteers meet the general inclusion criteria shared with the patient group but do not present MASLD or other cardiometabolic diseases and do not have any liver pathology.

Their participation serves as a control group for comparison with MASLD patients in the context of the study's biological and metabolic analyses.
Procedure: stool sampling, dietary assessment, and collection of blood and urine samples

MASLD group includes individuals receiving routine clinical care for liver-related conditions. During their scheduled medical visits, participants undergo standard clinical assessments and routine blood tests. Additional research-specific procedures-such as stool sampling, dietary assessment, and collection of blood and urine samples-are carried out without altering routine patient management. A fraction of blood sample is used for NAPA measurement. Stool samples are collected at home and returned directly to the Endocrinology, Diabetes and Nutrition Department within 24 hours after collection.

Healthy volunteers undergo the same research-specific procedures as patients but exclusively for research purposes, with no routine-care-related assessments.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Concentration of NAPA in Stool Culture Medium
Time Frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)
Quantification of the metabolite N-acetyl-phenylalanine (NAPA) in the culture medium of stool samples cultivated using the MiPro in vitro human gut microbiota culture system.
Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Concentration of Selected AAA-Derived Metabolites in Stool Culture Medium
Time Frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)
Quantification of selected aromatic amino acid (AAA)-derived metabolites in the culture medium of stool samples cultivated using the MiPro in vitro human gut microbiota culture system.
Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)
Gut Microbiota Composition in Stool Samples
Time Frame: Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)
Characterization of gut microbiota composition in stool samples who produce NAPA or other metabolites of interest, to identify bacterial species potentially involved in metabolite production. Microbiota profiling will be performed on a stool sample using bacterial DNA sequencing methods (16S rRNA gene sequencing or shotgun metagenomics).
Within 30 days after Visit 1 (sample collection and analysis performed at a single time point)
Concentration of NAPA in plasma
Time Frame: Baseline Visit 1 (sample collection and analysis performed at a single time point)
The quantification of NAPA level will be performed on plasma samples
Baseline Visit 1 (sample collection and analysis performed at a single time point)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hospices Civils de Lyon

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 11, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 17, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 31, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 3, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 2, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 69HCL25_1015

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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