NCT07488975

Developing Microbial Therapy for MASLD: From Mechanism to Clinical Validation

Development of Microbial Therapeutics for Metabolic Dysfunction-Associated Steatotic Liver Disease: From Mechanistic Investigations to Clinical Trials

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Leeuwenhoek Laboratories Co. Ltd. · Industry
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The aim of this study was to evaluate the effects of administering indigenously derived inactivated Akkermansia muciniphila (pAKK\_LWHK0003) on improving fatty liver in patients with metabolic dysfunction-associated steatotic liver disease (MASLD) and to assess its clinical safety.

Conditions

• Metabolic Dysfunction-Associated Steatotic Liver Disease

Interventions

Type	Name	Description
BIOLOGICAL	Pasteurized Akkermansia muciniphila LWHK0003_low dose	400 mg/capsule/days. Duration: 120 days
BIOLOGICAL	Pasteurized Akkermansia muciniphila LWHK0003_medium dose	400 mg/capsule/day. Duration: 120 days
BIOLOGICAL	Pasteurized Akkermansia muciniphila LWHK0003_high dose	400 mg/capsule/day. Duration: 120 days
OTHER	Placebo	400 mg/capsule/day. Duration: 120 days

Timeline

• Start date: 2025-01-22
• Primary completion: 2026-12-31
• Completion: 2026-12-31
• First posted: 2026-03-23
• Last updated: 2026-03-23

Locations

1 site across 1 country: Taiwan