Efficacy and Safety of Rifaximin in Treating MAFLD

Official title

Efficacy and Safety of Rifaximin in Treating Metabolic Associated Fatty Liver Disease: A Pilot Trial

Overview

Study Objective: to evaluate the efficacy and safety of rifaximin in the treatment of metabolic-associated fatty liver disease (MAFLD), and investigate the underlying mechanisms by which rifaximin influence MAFLD progression. Target Population: patients diagnosed with MAFLD. Intervention: this single-center, single-arm exploratory study will enroll up to 40 eligible MAFLD patients who meet the inclusion criteria, do not meet any exclusion criteria, and provide written informed consent. Participants will receive oral rifaximin at a dosage of 1200 mg/day (400 mg, three times daily) for 24 weeks. Patients will be advised to maintain their usual physical activity and adhere to a recommended dietary plan (e.g., Mediterranean diet). Concurrent therapies such as hepatoprotective agents, lipid-lowering medications, and antihypertensive treatments will remain unchanged, with close monitoring of relevant parameters. No additional prescription or over-the-counter drugs that may affect fatty liver progression or alter gut microbiota composition will be permitted during the study. The primary endpoint will be assessed at 24 weeks. If liver proton density fat fraction (PDFF) remains ≥ 8% after 24 weeks of rifaximin therapy, treatment will be extended for an additional 12 weeks, followed by reevaluation of PDFF changes. The maximum total treatment duration will not exceed 48 weeks. All patients will undergo a 24-week post-treatment follow-up period after discontinuation of rifaximin. Investigational Drug: Rifaximin (Alfa Wassermann S.p.A., Italy).

Interventions

• Drug Rifaximin (Xifaxan)
  Participants will receive oral rifaximin at a dosage of 1200 mg/day (400 mg, three times daily) for 24 weeks.

Primary outcome measures

• The change in liver fat content measured by MRI at 24 weeks of treatment. [Time frame: From enrollment to the end of treatment at 24 weeks]

Secondary outcome measures (12)

• Proportion of patients achieving ≥30% reduction in liver fat content measured by MRI-PDFF at 24 weeks of treatment compared to baseline [Time frame: From enrollment to the end of treatment at 24 weeks]
• The change in liver fat content measured by MRI-PDFF at 12 weeks of treatment. [Time frame: From enrollment to the end of treatment at 24 weeks]
• Proportion of patients achieving ≥30% reduction in liver fat content (PDFF) measured by MRI at 12 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 24 weeks]
• Changes in liver function indicators after 12 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 weeks]
• Changes in liver function indicators after 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 24 weeks]
• Change in liver fat content assessed via FibroScan after 12 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 weeks]
• Change in liver fat content assessed via FibroScan after 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 24 weeks]
• Changes in fatty liver index (FLI) after 12 and 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 and 24 weeks]
• Changes in NAFLD-liver fatty score（NAFLD-LFS）after 12 and 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 and 24 weeks]
• Changes in AST-to-Platelet Ratio Index (APRI) after 12 and 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 and 24 weeks]
• Changes in Fibrosis 4 (FIB-4) Score after 12 and 24 weeks of treatment [Time frame: From enrollment to the end of treatment at 12 and 24 weeks]
• Changes in NAFLD fibrosis score (NFS) after 12 and 24 weeks of treatment compared to baseline. [Time frame: From enrollment to the end of treatment at 12 and 24 weeks]

Eligibility criteria

Inclusion criteria

• Willing and able to provide written informed consent;
• Aged 18 to 75 years, regardless of gender;
• Diagnosed with fatty liver disease within the past 6 months;
• Presence of at least one of the following metabolic abnormalities:

(1) Overweight or obesity (BMI ≥23 kg/m²) (2) Type 2 diabetes (T2DM) (3) Clinical evidence of metabolic dysfunction (defined as meeting at least two of the following criteria): A. Waist circumference ≥90 cm for males or ≥80 cm for females B. Blood pressure ≥130/85 mmHg and/or diagnosed hypertension under treatment C. Fasting plasma triglycerides ≥1.7 mmol/L (150 mg/dL) or diagnosed hypertriglyceridemia under treatment D. Fasting HDL-C <1.0 mmol/L (40 mg/dL) for males or <1.3 mmol/L (50 mg/dL) for females, or diagnosed dyslipidemia under treatment E. Prediabetes: fasting glucose 5.6-6.9 mmol/L (100-125 mg/dL) or 2-hour postprandial glucose 7.8-11.0 mmol/L (140-199 mg/dL) or HbA1c 5.7%-6.4% (39-47 mmol/mol) F. Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score ≥2.5 G. Plasma high-sensitivity C-reactive protein (hs-CRP) >2 mg/L 5. Liver fat content ≥8% as measured by MRI proton density fat fraction (MRI-PDFF).

Exclusion criteria

• Cirrhosis - Confirmed by clinical, laboratory, imaging, and/or liver biopsy.
• Chronic liver disease of other etiologies (e.g., viral/autoimmune hepatitis, alcoholic liver disease, drug-induced liver injury)
• Secondary hepatic steatosis (e.g., drug-induced, total parenteral nutrition-related, or hypothyroidism-associated);
• Recent use of intestinal flora-modifying agents, or unstable regimens of medications (including hepatoprotectants, metformin, thiazolidinediones, fibrates, statins, et al) within 4 weeks prior to enrollment;
• Agents with potential effects on MAFLD progression administered within 12 weeks prior to enrollment, excluding those maintained at stable doses for ≥24 weeks (e.g., Glucagon-like peptide-1 receptor agonists, Dipeptidyl peptidase IV inhibitors, Obeticholic acid, Sodium-glucose cotransporter 2 inhibitors, Resmetirom or anti-obesity medications)
• Poorly controlled diabetes (HbA1c >9%)
• Jaundice (total bilirubin ≥85 μmol/L), or Renal dysfunction (serum creatinine ≥1.2 × ULN)
• History of bariatric surgery
• Active or suspected malignancy
• Severe systemic conditions - Including: Inflammatory diseases (e.g., connective tissue disorders), Biliary/pancreatic disorders, Chronic/acute infections, Severe cardiovascular, pulmonary, or hematologic diseases, Myocardial infarction or stroke within 6 months, Psychiatric disorders
• HIV infection
• Known hypersensitivity to rifaximin
• MRI contraindications - Including: Metal implants, Claustrophobia, Body size exceeding scanner capacity
• Pregnancy, lactation, or planned pregnancy
• Participation in another drug trial within 3 months
• Other conditions deemed unsuitable by investigators

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Changzheng Hospital, Naval Medical University, shanghai, China — Shanghai

Identifiers

NCT: NCT07185932 · CZXH2021001.02

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗