Efficacy and Safety of Rifaximin in Treating MAFLD

NCT07185932 | Recruiting Early Phase 1

• 1 other identifier: CZXH2021001.02
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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).

Conditions

Metabolic-associated Fatty Liver Disease

Keywords

metabolic-associated fatty liver disease; Rifaximin

Outcome Measures

Primary Outcomes (1)

• 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.

  From enrollment to the end of treatment at 24 weeks

Secondary Outcomes (22)

• Proportion of patients achieving ≥30% reduction in liver fat content measured by MRI-PDFF at 24 weeks of treatment compared to baseline

  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.

  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.

  From enrollment to the end of treatment at 24 weeks

• Changes in liver function indicators after 12 weeks of treatment compared to baseline.

  From enrollment to the end of treatment at 12 weeks

• Changes in liver function indicators after 24 weeks of treatment compared to baseline.

  From enrollment to the end of treatment at 24 weeks

Other Outcomes (1)

• Changes in liver fat content assessed via MRI-PDFF during extended treatment (36 or 48 weeks) and at 12/24 weeks post-treatment.

  Through study completion, an average of 3 years

Study Arms (1)

Rifaximin treatment group

EXPERIMENTAL

Participants will receive oral rifaximin.

Drug: Rifaximin (Xifaxan)

Interventions

Rifaximin (Xifaxan) DRUG

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

Rifaximin treatment group

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Shanghai Changzheng Hospital: lead

Study Sites (1)

Changzheng Hospital, Naval Medical University, shanghai, China

Shanghai, Shanghai Municipality, 200003, China

RECRUITING

MeSH Terms

Interventions

Rifaximin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Central Study Contacts

CHUAN YIN, M.D.

CONTACT

+8613482705212; ilse1225@163.com

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Department of Gastroenterology, Changzheng Hospital

Model Details: Participants will receive oral rifaximin at a dosage of 1200 mg/day (400 mg, three times daily) for 24 weeks.

Study Record Dates

• First Submitted: August 21, 2025
• First Posted: September 22, 2025
• Study Start: August 10, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: September 22, 2025

Record last verified: 2025-09

Locations

CN (1)