NCT07185932 - Efficacy and Safety of Rifaximin in Treating MAFLD | Crick

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Willing and able to provide written informed consent; 2. Aged 18 to 75 years, regardless of gender; 3. Diagnosed with fatty liver disease within the past 6 months; 4. 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 1. Cirrhosis - Confirmed by clinical, laboratory, imaging, and/or liver biopsy. 2. Chronic liver disease of other etiologies (e.g., viral/autoimmune hepatitis, alcoholic liver disease, drug-induced liver injury) 3. Secondary hepatic steatosis (e.g., drug-induced, total parenteral nutrition-related, or hypothyroidism-associated); 4. 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; 5. 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) 6. Poorly controlled diabetes (HbA1c \>9%) 7. Jaundice (total bilirubin ≥85 μmol/L), or Renal dysfunction (serum creatinine ≥1.2 × ULN) 8. History of bariatric surgery 9. Active or suspected malignancy 10. 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 11. HIV infection 12. Known hypersensitivity to rifaximin 13. MRI contraindications - Including: Metal implants, Claustrophobia, Body size exceeding scanner capacity 14. Pregnancy, lactation, or planned pregnancy 15. Participation in another drug trial within 3 months 16. Other conditions deemed unsuitable by investigators

Outcomes

Primary Outcomes

The change in liver fat content measured by MRI at 24 weeks of treatment.

Absolute and relative changes in MRI-measured liver proton density fat fraction (PDFF) at 24 weeks compared to baseline.

Time frame: From enrollment to the end of treatment at 24 weeks

Secondary Outcomes

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.

Absolute and relative changes in MRI-measured liver PDFF at 12 weeks compared to baseline.

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.

The proportion of patients whose liver fat content (PDFF), assessed via MRI, decreased by ≥30% from baseline after 12 weeks of treatment.

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.

Changes in liver function parameters from baseline after 12 weeks of treatment.

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.

Change in controlled attenuation parameter (CAP) values, measured by FibroScan, from baseline after 12 weeks of therapy

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.

Change in controlled attenuation parameter (CAP) values, measured by FibroScan, from baseline after 24 weeks of therapy

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.

FLI is utilized to assess the severity of hepatic steatosis. Its calculation formula is based on laboratory and anthropometric measurements, including triglyceride (TG) and gamma-glutamyl transferase (GGT) levels, body mass index (BMI), and waist circumference (WC). FLI = (e\^(0.953 \* ln(triglycerides) + 0.139 \* BMI + 0.718 \* ln(ggt) + 0.053 \* waist circumference - 15.745)) / (1 + e\^(0.953 \* ln(triglycerides) + 0.139 \* BMI + 0.718 \* ln(ggt) + 0.053 \* waist circumference - 15.745)) \* 100 A FLI value below 30 can be used to rule out steatosis (sensitivity = 87%; negative likelihood ratio \[LR-\] = 0.2), while a FLI value equal to or above 60 can be used to rule in hepatic steatosis.