MASLD Butyrate Supplementation Treatment Efficacy Review (MASTER)

December 29, 2024 updated by: Miloš Mitrović, MD, University Medical Center Zvezdara

Exploring the Potential of Oral Butyrate Supplementation in Metabolic Dysfunction-Assosciated Steatotic Liver Disease Patients

  1. Study Design This is an interventional study designed to evaluate the efficacy of oral butyrate supplementation in patients diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD).
  2. Introduction MASLD is becoming an increasingly significant global public health issue, though the underlying mechanisms of this disorder are not fully understood. Emerging research highlights the crucial role of the gut microbiota, particularly through the production of short-chain fatty acids such as butyrate, in regulating metabolic processes related to MASLD. Animal studies have shown that butyrate has beneficial effects on liver function, but large-scale human studies exploring this potential are lacking. Butyrates have long been used in the treatment of irritable bowel syndrome without significant adverse effects.

  3. Study Objectives

    Primary Objective:

    To assess the impact of oral butyrate supplementation on liver steatosis in patients with MASLD, measured by changes in the attenuation coefficient (ATT) using point shear wave elastography (pSWE).

    Secondary Objectives:

    • Evaluate changes in alanine aminotransferase (ALT) levels.
    • Assess the impact on inflammatory markers (high-sensitivity C-reactive protein [hsCRP], tumor necrosis factor-alpha [TNF-α], interleukin-1, interleukin-6, and cytokeratin-18).
    • Measure changes in lipid profile and stool short-chain fatty acids (SCFA).
    • Evaluate microRNA expression (miR-192, miR-885, miR-122).

  4. Methods/Study Design 4.1 Study Population and Inclusion Criteria

    Inclusion Criteria:

    • Patients aged 18-70 years with confirmed MASLD based on:

      • ATT > 0.63 dB/cm/MHz measured by pSWE.
      • ALT level > 40 IU/L.
    • Patients capable of providing informed consent.

    Exclusion Criteria:

    • History of other liver diseases (e.g., viral hepatitis, alcoholic liver disease).
    • Current use of medications known to affect liver function (e.g., statins, corticosteroids).
    • Pregnant and breastfeeding women. 4.2 Sample Size and Power Calculation The study will include 200 patients with MASLD, randomly assigned in a 1:1 ratio to receive either calcium butyrate or sodium butyrate. A sample size of 200 patients was determined to ensure sufficient power to detect significant differences in primary and secondary outcomes with an alpha value of 0.05 and 80% power.

    4.3 Randomization and Blinding Participants will be randomly assigned to two groups using computer-generated randomization. The study will be single-blind, meaning that patients will not know which type of butyrate they receive.

    4.4 Interventions

    • Group 1 (Calcium Butyrate): 1000 mg/day calcium butyrate.
    • Group 2 (Sodium Butyrate): 1000 mg/day sodium butyrate.
    • Both groups will follow a Mediterranean diet (20-30 kcal/kg body weight; 35-40% fats, 20% protein, 40-45% carbohydrates).
    • Treatment will last for 12 weeks. 4.5 Outcome Measures

    Primary Outcome:

    • Change in liver steatosis measured by ATT after 12 weeks compared to baseline.

    Secondary Outcomes:

    • Changes in ALT, inflammatory markers (hsCRP, TNF-α, IL-1, IL-6, cytokeratin-18), lipid profile, and stool SCFA levels.
    • Changes in microRNA expression (miR-192, miR-885, miR-122).

  5. Data Collection and Analysis 5.1 Data Collection At baseline and after 12 weeks, the following assessments will be conducted:

    • Liver steatosis measured by pSWE.
    • Blood samples for ALT, inflammatory markers, and lipid profile.
    • Stool samples for SCFA analysis.
    • MicroRNA panel analysis (miR-192, miR-885, miR-122). 5.2 Statistical Analysis Data will be analyzed using SPSS software (v. XX). Baseline and 12-week data will be compared using paired t-tests or Wilcoxon tests. ANOVA will be used to assess differences between groups. Statistical significance will be set at p < 0.05.
  6. Ethics and Dissemination 6.1 Ethical Considerations The study protocol has been submitted for review by the Ethics Committee of the Clinical Center of Serbia, Belgrade. Written consent will be obtained from all participants.

6.2 Data Management All patient data will be anonymized, securely stored, and managed following local data protection regulations.

6.3 Dissemination The study results will be published in peer-reviewed scientific journals and presented at international conferences. No commercial application of the results is planned.

Study Overview

Status

Enrolling by invitation

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

200

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Serbia
      • Belgrade, Serbia, 11000
        • University Medical Center Zvezdara

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients aged over 18 years with confirmed MASLD based on:

ATT > 0.63 dB/cm/MHz measured by pSWE.

ALT level > 40 IU/L.

  • Patients capable of providing informed consent.

Exclusion Criteria:

  • History of other liver diseases (e.g., viral hepatitis, alcoholic liver disease).
  • Current use of medications known to affect liver function (e.g., statins, corticosteroids).
  • Pregnant and breastfeeding 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: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Sodium Butyrate Arm
1000 mg/day Sodium butyrate in combination with a Mediterranean diet during 12 weeks
Drug: Sodium-Butyrate
1000 mg/day of sodium-butyrate
Other Names:
  • Colosal
Active Comparator: Calcium Butyrate Arm
1000 mg/day calcium butyrate in combination with a Mediterranean diet during 12 weeks
Drug: Calcium Butyrate
1000 mg/day of calcium-butyrate
Other Names:
  • Dibuzin

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in liver steatosis measured by ATT after 12 weeks compared to baseline
Time Frame: 12 weeks
Liver steatosis is going to be assessed by the attenuation coefficient (ATT) on ultrasound B mode at two points- before the treatment and after the last drug dose, and define the absolute and relative change of this parameter.
12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in ALT and serum inflammatory markers (hsCRP, TNF-α, IL-1, IL-6, cytokeratin-18), lipid profile
Time Frame: 12 weeks
Absolute and relative changes in ALT, inflammatory markers (hsCRP, TNF-α, IL-1, IL-6, cytokeratin-18), lipid profile between baseline and endpoint values will be assessed
12 weeks
Changes in stool SCFA levels.
Time Frame: 12 weeks
Absolute and relative changes in stool SCFA levels between baseline and endopint will be assessed
12 weeks

Collaborators and Investigators

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

Sponsor

University Medical Center Zvezdara

Investigators

  • Principal Investigator: Miloš V Mitrović, MD PhD, University Medical Center Zvezdara

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

January 4, 2024

Primary Completion (Estimated)

December 31, 2024

Study Completion (Estimated)

January 20, 2025

Study Registration Dates

First Submitted

December 29, 2024

First Submitted That Met QC Criteria

December 29, 2024

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

December 29, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 1.11.24.

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Will make figshare.com repository of data, excluding patients personal data, and share it within publication

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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.

Clinical Trials on MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease

Clinical Trials on Sodium-Butyrate

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Congo, DR of

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe