MASLD Butyrate Supplementation Treatment Efficacy Review

NCT06759363 | Unknown Phase 3 DMC

• 1 other identifier: 1.11.24.
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

• 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).
• Methods/Study Design 4.1 Study Population and 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).
• 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.
• 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.

Conditions

MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease

Keywords

Butyrate supplementation; MASLD; Inflammation

Outcome Measures

Primary Outcomes (1)

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

  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 Outcomes (2)

• Changes in ALT and serum inflammatory markers (hsCRP, TNF-α, IL-1, IL-6, cytokeratin-18), lipid profile

  12 weeks

• Changes in stool SCFA levels.

  12 weeks

Study Arms (2)

Sodium Butyrate Arm

ACTIVE COMPARATOR

1000 mg/day Sodium butyrate in combination with a Mediterranean diet during 12 weeks

Drug: Sodium-Butyrate

Calcium Butyrate Arm

ACTIVE COMPARATOR

1000 mg/day calcium butyrate in combination with a Mediterranean diet during 12 weeks

Drug: Calcium Butyrate

Interventions

Sodium-Butyrate DRUG

1000 mg/day of sodium-butyrate

Also known as: Colosal

Sodium Butyrate Arm

Calcium Butyrate DRUG

1000 mg/day of calcium-butyrate

Also known as: Dibuzin

Calcium Butyrate Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University Medical Center Zvezdara: lead

Study Sites (1)

University Medical Center Zvezdara

Belgrade, Serbia, 11000, Serbia

Location

Related Publications (1)

• Fogacci F, Giovannini M, Di Micoli V, Grandi E, Borghi C, Cicero AFG. Effect of Supplementation of a Butyrate-Based Formula in Individuals with Liver Steatosis and Metabolic Syndrome: A Randomized Double-Blind Placebo-Controlled Clinical Trial. Nutrients. 2024 Jul 28;16(15):2454. doi: 10.3390/nu16152454.

  PMID: 39125336 BACKGROUND

MeSH Terms

Conditions

Inflammation

Interventions

Butyric Acid

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Butyrates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids, Volatile; Fatty Acids; Lipids

Study Officials

• Miloš V Mitrović, MD PhD

  University Medical Center Zvezdara

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Miloš Mitrović- digestive disease specialist at Gastroenterology and Hepatology Unit of Internal Medicine Clinic of University Medical center

Study Record Dates

• First Submitted: December 29, 2024
• First Posted: January 6, 2025
• Study Start: January 4, 2024
• Primary Completion: December 31, 2024
• Study Completion: January 20, 2025
• Last Updated: January 6, 2025

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will share

Locations

SE (1)