Rifaximin-α treatment for metabolic dysfunction‑associated steatotic liver disease

Efficacy and Safety of Rifaximin-α in the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized, Open-Label, Controlled Pilot Clinical Trial

This trial will test whether taking Rifaximin‑α daily for 24 weeks can reduce liver fat and improve metabolic markers in adults with MASLD.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Shanghai Changzheng Hospital (Academic / other)
• Drugs / interventions: methotrexate
• Locations: 1 site (Shanghai)
• Trial ID: NCT07381257 on ClinicalTrials.gov

What this trial studies

This is a multicenter, prospective, randomized, controlled early phase 1 trial enrolling adults with MASLD and MR‑PDFF ≥ 8%. Participants will be randomized 2:1 to receive oral Rifaximin‑α 1200 mg/day or control for 24 weeks, with all participants advised on physical activity and a Mediterranean-style diet. After treatment, patients will be followed for an additional 24 weeks to monitor safety, liver fat changes, metabolic outcomes, and exploratory mechanistic biomarkers. The trial also aims to explore how Rifaximin‑α may modify gut-liver mechanisms that contribute to MASLD progression.

Who should consider this trial

Good fit: Adults aged 18–75 with imaging-confirmed hepatic steatosis (MR‑PDFF ≥ 8%) plus at least one metabolic or cardiovascular risk factor who can provide informed consent are the intended participants.

Not a fit: People without significant hepatic steatosis by MR‑PDFF, those outside the 18–75 age range, those lacking the listed metabolic risk factors, or individuals with contraindications to rifaximin are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, Rifaximin‑α could reduce liver fat and slow disease progression, potentially improving liver-related and metabolic outcomes for patients with MASLD.

How similar studies have performed: Previous small or exploratory studies of rifaximin in fatty liver disease have shown mixed or preliminary signals but no definitive, large-scale proof of benefit to date.

Eligibility criteria

Inclusion Criteria

1. Willingness to provide written informed consent.
2. Aged 18 to 75 years, inclusive, regardless of gender.
3. Diagnosis of hepatic steatosis (fatty liver) within the past 6 months.
4. Presence of at least one metabolic/cardiovascular risk factor:

   A. BMI ≥ 23.0 kg/m², or waist circumference ≥ 90 cm (male) / 80 cm (female). B. Fasting plasma glucose (FPG) ≥ 5.6 mmol/L, or 2-hour postprandial glucose ≥ 7.8 mmol/L, or HbA1c ≥ 5.7%, or documented history of type 2 diabetes mellitus (T2DM) or current use of anti-diabetic medication.

   C. Fasting serum triglycerides (TG) ≥ 1.70 mmol/L, or current use of medication for hypertriglyceridemia.

   D. Serum high-density lipoprotein (HDL) cholesterol ≤ 1.0 mmol/L (male) and ≤ 1.3 mmol/L (female), or current use of lipid-lowering medication.

   E. Blood pressure ≥ 130/85 mmHg, or current use of antihypertensive medication.
5. Liver fat content ≥ 8% as measured by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF).

Exclusion Criteria

1. Confirmed diagnosis of liver cirrhosis based on clinical, laboratory, imaging, and/or liver biopsy findings.
2. Evidence of other specific etiologies of chronic liver disease confirmed by history or laboratory tests, including but not limited to: viral hepatitis (B or C, etc.), autoimmune liver disease, alcohol-related liver disease (defined as \>20 g/day for females or \>30 g/day for males), drug-induced liver injury, Wilson's disease, alpha-1 antitrypsin deficiency, or hereditary hemochromatosis.
3. Other identifiable causes of hepatic steatosis confirmed by history or laboratory tests, such as: specific medications (e.g., tamoxifen, amiodarone, valproate, methotrexate, glucocorticoids, olanzapine), total parenteral nutrition, hypothyroidism, inflammatory bowel disease, Cushing's syndrome, celiac disease, abetalipoproteinemia, lipodystrophic diabetes, Mauriac syndrome, hypopituitarism, hypogonadism, polycystic ovary syndrome, etc.
4. Use of medications known to alter gut microbiota (e.g., lactulose, systemic antibiotics, any intestinal microecological preparations) within 4 weeks prior to screening.
5. Dose of hepatoprotective or lipid-lowering medications not stabilized for at least 4 weeks prior to screening.
6. Received any Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or remeglutide treatment within 12 weeks prior to screening, or plans to receive such treatment during the study.
7. Dose of medications that may affect MASLD, anti-diabetic agents (excluding GLP-1 RAs and remeglutide), or weight-loss drugs not stabilized for at least 12 weeks prior to screening.
8. Self-reported weight change \>5% within 4 weeks prior to screening.
9. BMI \> 35 kg/m².
10. Poorly controlled glycemia: HbA1c \> 9%.
11. Total bilirubin \> 1.5 mg/dL (except with normal direct bilirubin), or Alanine Aminotransferase (ALT) \> 5 times the Upper Limit of Normal (ULN), or Aspartate Aminotransferase (AST) \> 5 times ULN, or Alkaline Phosphatase (ALP) \> 2 times ULN.
12. Estimated Glomerular Filtration Rate (eGFR) \< 30 mL/min/1.73 m².
13. History of or planned bariatric/metabolic therapy, including but not limited to endoscopic interventions, surgical procedures, or Traditional Chinese Medicine therapies. Exceptions may be made if previous interventions have been reversed or removed (e.g., intragastric balloon, subcutaneous threads) for more than 12 weeks.
14. History of or current hepatocellular carcinoma (HCC).
15. Diagnosis of any malignancy within the past 5 years, except for malignancies with low risk of metastasis or death (estimated 5-year overall survival \>90%), such as effectively treated early-stage gastrointestinal cancer, carcinoma in situ of the cervix, non-melanoma skin cancer, or localized prostate cancer.
16. Significant comorbid conditions affecting the cardiovascular, respiratory, rheumatological/immunological, hematological, biliary, or pancreatic systems; or history of myocardial infarction, stroke, heart failure, unstable angina, or transient ischemic attack within 6 months prior to screening; or presence of psychiatric disorders.
17. HIV infection.
18. Known allergy or hypersensitivity to rifaximin.
19. Contraindications to MRI, such as incompatible metallic implants, claustrophobia, or body size exceeding scanner capacity.
20. Pregnant or lactating women, women of childbearing potential not using effective contraception, or individuals planning pregnancy.
21. Participation in another investigational drug trial within 3 months prior to screening.
22. Any other condition deemed by the investigator to be unsuitable for participation in the study.

Where this trial is running

Shanghai

• Changzheng Hospital, Naval Medical University, shanghai, China — Shanghai, China (Recruiting)

Study contacts

• Principal investigator: Wei Fen Xie, Director — Department of Gastroenterology, Changzheng Hospital, Shanghai Changzheng Hospital
• Study coordinator: Chuan Yin, M.d.

Conditions Metabolic Dysfunction-Associated Steatotic Liver Disease; Rifaximin