Investigation on Safety and Efficacy of Soybean Fermented Extract (MBS217) in Treating Patients With NAFLD

Investigation on Safety and Efficacy of Soybean Fermented Extract (MBS217) in Treating Patients With Non-alcoholic Fatty Liver Disease: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Study in National Taiwan University Hospital

Investigators aimed to investigate the efficacy and safety of fermented soybean extract (MBS-217) in treating participants with Non-alcoholic fatty liver disease (NAFLD) in this study.

Study Overview

• Status: Not yet recruiting
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: MBS217; Dietary supplement: Placebo

Detailed Description

Background: NAFLD is one of the most prevalent chronic liver diseases in Taiwan. NAFLD can progress to fibrosis, cirrhosis, and even liver cancer. Based on the current trend in epidemiology, fatty liver disease is forecasted to be the leading cause of liver transplantation by 2030. Since NAFLD imposes a significant medical burden and there is no approved medication for NAFLD, developing an effective therapy for improving NAFLD is undoubtedly an unmet need. Diet and gut microbiota play pivotal roles in NAFLD progress. The composition of the gut microbiota and gut barrier function is affected by dietary factors, which cause pathophysiological impacts on the liver through the immune and metabolic communications between gut and liver, which is coined as the "gut-liver axis." Therefore, intervention with dietary products from probiotics and prebiotics may be an opportunity to develop effective therapy against NAFLD. In fact, current evidence has shown that fermented soybean products can modulate hepatic lipid metabolism and possess potential prebiotic activities. Also, our preliminary data have shown that MBS217 supplementation has the effects of modulating gut microbiota and regulating the hepatic inflammatory-related immune response in both nonalcoholic steatohepatitis (NASH) mice and healthy adult subjects. Objective: Investigators aimed to investigate the efficacy and safety of MBS217 in treating participants with NAFLD in this study. The changes in other metabolic parameters, gut microbiome, metabolomics, and gut permeability will also be investigated. Methods: Using a block randomization with a block size of 2 in a 1:1 ratio, 30 eligible adult subjects aged 20-70 years diagnosed with NAFLD will be randomized to receive one of the following regimens. This study plans to enroll 30 eligible adult subjects aged 20-70 years diagnosed with NAFLD. Enrolled subjects will be randomly assigned to receive 4 mL of either MBS217 or placebo (1:1) treatment for 16 weeks and then followed for 8 weeks, with assessment for NAFLD-related parameters, gut microbiome, metabolomics, and gut permeability. Outcome analysis: The primary outcome is the improvement of hepatic steatosis, fibrosis, stiffness, and FIB-4 evaluated by FibroScan or MRI. The secondary outcomes are the frequency of adverse events, the overall NAFLD-related parameters, gut microbiota, metabolomics, and gut permeability.

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Wei-Kai Wu; Phone Number: +886233667316; Email: weikaiwu0115@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged between 20 and 70 years old.
• Serum ALT of the subject is between 40-200 U/L.
• The subject is diagnosed as NAFLD through FibroScan (CAP > 220 db/m).
• BMI of the subject is between 18.5-40 kg/m2.
• The subject is able to provide written informed consent by himself/herself and agrees to comply with all protocol requirements.
• The subject agrees to comply with the following two requirements:

comply with all follow-up visit requirements according to the trial protocol. comply with all requirement regarding fecal samples collection, storage and delivery according to the trial protocol.

• If the subject is reproductive women, she should agree to take more than two ways of contraceptive methods.

Exclusion Criteria:

• The subject is pregnant or lactating.
• The subject has received any antibiotic (excluding topical agents), antifungals or antivirals within 30 days prior to visit 1.
• The subject has received any steroids (excluding topical agents), immunosuppressant or anti-inflammation drugs within 14 days prior to visit 1.
• The subject has received probiotics or prebiotics 14 days prior to visit 1.
• The subject has received medication affecting evaluating indicators, including hepatitis and lipid metabolism related compounds, but excluding the following medicines: Statins, Fibrates, Silymarin, N-Acetyl Cystein, Thiazolidinediones, Metformin, Fibrate, Cholestyramine, Ezetimibe, Orlistat, SGLT2i and GLP1-RAs.
• The subject has a clinically significant, currently active or underlying diarrhea (loose stools more than three times in 24 hours) of infectious etiologies.
• The subject who has been diagnosed a severe/injury hepatic disease, acute/chronic viral hepatitis B, acute/chronic viral hepatitis C, human immunodeficiency virus infection, disease affecting liver function, active inflammatory bowel disease, gastric ulcer, chronic kidney disease, kidney function repairmen, chronic gut inflammatory disease, coronary artery disease with arterial stent surgery in half year, cancer, autoimmune disease, fasting glucose≥ 300 mg/dl, HbA1c>9%, or serum triglyceride≥ 500 mg/dl.
• The subject currently is participating in studies involving other investigational drugs, medical devices, functional foods, or cosmetic within 30 days prior to visit 1.
• The subject has participated in body weight control plan within 60 days prior to visit 1.
• The subject has an alcohol abuse problem.
• The subject has been aboard for 10 days within 60 days prior to visit 1, or plans to go aboard during this study.
• The subject has soybean allergy.
• The subject is vegetarian or special diet.
• The subject is considered by the investigator as not suitable for the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: MBS-217; 4 ml MBS-217 twice a day for 16 weeks	Dietary supplement: MBS217; Soybean Fermented Extract (MBS217)
Placebo Comparator: Placebo; 4 ml MBS-217 placebo twice a day for 16 weeks	Dietary supplement: Placebo; Without active ingredient

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in gut microbiota	evaluated by fecal 16S rRNA gene sequencing	baseline to 8th, 12th, 16th and 24th weeks
Improvement of intrahepatic fibrosis	evaluated by FibroScan	baseline to 16th and 24th weeks
Changes in hepatic steatosis composition	evaluated by MRI-PDFF and MRI-MRS	baseline to 16th week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in FIB-4	Fibrosis-4 (FIB-4) Index	baseline to 12th, 16th and 24th weeks
Changes in gut permeability	evaluated by lactulose/mannitol ratio	baseline to 16th week

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Taipei Medical University Hospital

Publications and helpful links

General Publications

• Huang SC, Su HJ, Kao JH, Tseng TC, Yang HC, Su TH, Chen PJ, Liu CJ. Clinical and Histologic Features of Patients with Biopsy-Proven Metabolic Dysfunction-Associated Fatty Liver Disease. Gut Liver. 2021 May 15;15(3):451-458. doi: 10.5009/gnl20218.

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): April 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: December 21, 2022
• First Submitted That Met QC Criteria: January 8, 2023
• First Posted (Estimate): January 16, 2023

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 8, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 202108126RIPB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No