Developing Microbial Therapy for MASLD: From Mechanism to Clinical Validation

NCT07488975 · tracked via the Priya Life Science Taiwan tracker

Sponsor

Leeuwenhoek Laboratories Co. Ltd

Phase

Phase 1

Started

2025-01-22

Last updated

2026-08-26

Condition(s) studied

Metabolic Dysfunction-Associated Steatotic Liver Disease

Investigational drug(s) / intervention(s)

Pasteurized Akkermansia muciniphila LWHK0003_low dosePasteurized Akkermansia muciniphila LWHK0003_medium dosePasteurized Akkermansia muciniphila LWHK0003_high dosePlacebo

Pasteurized Akkermansia muciniphila LWHK0003_low dose: 400 mg/capsule/days. Duration: 120 days

Pasteurized Akkermansia muciniphila LWHK0003_medium dose: 400 mg/capsule/day. Duration: 120 days

Pasteurized Akkermansia muciniphila LWHK0003_high dose: 400 mg/capsule/day. Duration: 120 days

Placebo: 400 mg/capsule/day. Duration: 120 days

Study summary

Metabolic dysfunction-associated steatotic liver disease (MASLD), redefined in 2020, is an improved diagnostic standard evolved from non-alcoholic fatty liver disease (NAFLD), emphasizing the correlation between hepatic steatosis and metabolic dysfunction. Compared to NAFLD, which relies on exclusion-based diagnosis, MASLD criteria enhance population homogeneity in studies and accommodate patients with coexisting liver diseases, thereby improving the efficiency and relevance of drug development. MASLD affects approximately one-quarter of the global population. If left untreated, it may progress to liver fibrosis, cirrhosis, or hepatocellular carcinoma. Given its high clinical burden and the current lack of FDA-approved therapies, effective treatments for MASLD are urgently needed.

Previous studies suggest that diet and gut microbiota play crucial roles in the pathogenesis of MASLD. Dietary composition influences microbial balance and intestinal barrier function. In dysbiosis, gut-derived harmful substances such as pathogen-associated molecular patterns (PAMPs) and microbiota-derived metabolites (MDMs) may translocate via a leaky gut to the liver through the portal vein, contributing to hepatic injury. These processes, often described as the gut-liver axis, remain incompletely understood.

Animal studies have shown that dietary components regulating gut microbiota may help alleviate MASLD. While clinical evidence remains limited, incorporating microbiota-modulating and immune-regulating food ingredients holds potential. Next-generation probiotics have demonstrated benefits in improving hepatic lipid metabolism and modulating gut microbiota, potentially slowing MASLD progression through gut-liver axis modulation.

Our previous research investigated a pasteurized Akkermansia muciniphila strain, NTUH\_Amuc03 (pAKK\_LWHK0003), which attenuated fatty liver progression in preclinical models. In mice subjected to a high-fat, high-fructose, high-cholesterol diet, pAKK\_LWHK0003 administration resulted in reduced body weight, improved dyslipidemia, lowered NAFLD activity scores, and improved HOMA-IR. These findings support the potential of pAKK\_LWHK0003 in slowing MASLD progression.

This study aims to evaluate further the clinical efficacy and safety of pAKK\_LWHK0003 in individuals with MASLD.

Eligibility

Sex

ALL

Min age

18 Years

Max age

70 Years

Healthy volunteers

Inclusion Criteria: * Fibroscan，CAP ≧ 260db/m Exclusion Criteria: A. Pregnant women or women who are breastfeeding. B. Use of probiotics and prebiotic-related products (including yogurt, yogurt, Yakult, etc.) within 14 days before the screening visit. C. Patients who have used antibiotics (except skin lotions) or antifungal drugs within 30 days before the screening visit. D. Use of glucagon-like peptide-1 receptor agonists (GLP1-RAs) within six months prior to the screening visit. E. Use of drugs that may affect the evaluation index within 14 days before the screening visit, during the screening visit, or during the planned trial period, such as steroids, immunosuppressants, or anti-inflammatory drugs, or drugs containing ingredients for treating hepatitis or affecting fat metabolism, including HMG-CoA reductase inhibitors (statins), fibrates, silymarin, thiazolidinediones, metformin, cholestyramine, ezetimibe, orlistat, and sodium-glucose transporter type 2 inhibitors (SGLT2i). This restriction does not apply if the above-mentioned drugs have been used continuously for more than six months and the dosage is not changed during the trial. F. Those who have had severe gastrointestinal infection diarrhea symptoms within 14 days before the screening visit (more than three watery stools in 24 hours). G. Have the following medical history or laboratory abnormalities:

Primary outcome measure(s)

Liver steatosis, fibrosis, liver stiffness, and FIB-4 index — From enrollment to the end of treatment, up to 52 weeks
To assess the statistical differences between baseline and Weeks 12 and 16 (Visit V5 and V6) after administration of placebo or different doses (10⁹, 10¹⁰, 10¹¹ CFU) of pAKK LWHK0003 capsules, in terms of liver fat content (steatosis), fibrosis, liver stiffness, and FIB-4 index as measured by FibroScan and MRI/MRE.

Trial sites (1)

Facility	City	Region	Status
National Taiwan University Hospital	Taipei	Taiwan

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT07488975 on ClinicalTrials.gov ↗ ← All trials in Taiwan