Developing Microbial Therapy for MASLD: From Mechanism to Clinical Validation

NCT07488975 | Recruiting Phase 1

• 1 other identifier: LL-IRB-2403
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metabolic Dysfunction-Associated Steatotic Liver Disease

Keywords

MASLD; MASH

Outcome Measures

Primary Outcomes (1)

• Liver steatosis, fibrosis, liver stiffness, and FIB-4 index

  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.

  From enrollment to the end of treatment, up to 52 weeks

Study Arms (4)

Pasteurized Akkermansia muciniphila LWHK0003 _low dose

EXPERIMENTAL

400 mg/capsule/day. Duration: 120 days

Biological: Pasteurized Akkermansia muciniphila LWHK0003_low dose

Pasteurized Akkermansia muciniphila LWHK0003 _medium dose

EXPERIMENTAL

400 mg/capsule/day. Duration: 120 days

Biological: Pasteurized Akkermansia muciniphila LWHK0003_medium dose

Pasteurized Akkermansia muciniphila LWHK0003 _high dose

EXPERIMENTAL

400 mg/capsule/day. Duration: 120 days

Biological: Pasteurized Akkermansia muciniphila LWHK0003_high dose

Placebo

PLACEBO COMPARATOR

400 mg/capsule/day. Duration: 120 days

Other: Placebo

Interventions

Pasteurized Akkermansia muciniphila LWHK0003_low dose BIOLOGICAL

400 mg/capsule/days. Duration: 120 days

Pasteurized Akkermansia muciniphila LWHK0003 _low dose

Placebo OTHER

400 mg/capsule/day. Duration: 120 days

Placebo

Pasteurized Akkermansia muciniphila LWHK0003_medium dose BIOLOGICAL

400 mg/capsule/day. Duration: 120 days

Pasteurized Akkermansia muciniphila LWHK0003 _medium dose

Pasteurized Akkermansia muciniphila LWHK0003_high dose BIOLOGICAL

400 mg/capsule/day. Duration: 120 days

Pasteurized Akkermansia muciniphila LWHK0003 _high dose

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Fibroscan，CAP ≧ 260db/m

You may not qualify if:

• 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:

Sponsors & Collaborators

• Leeuwenhoek Laboratories Co. Ltd.: lead

Study Sites (1)

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2025
• First Posted: March 23, 2026
• Study Start: January 22, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 23, 2026

Record last verified: 2025-05

Locations

TW (1)