NCT07381257招募中1 期
Efficacy and Safety of Rifaximin-α in the Treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease: A Randomized, Open-Label, Controlled Pilot Clinical Trial
干预措施
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- The relative change in liver fat content measured by MRI from baseline to 24 weeks.
研究概览
简要总结
Study Objective: To evaluate the efficacy and safety of Rifaximin-α in the treatment of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), and investigate the underlying mechanisms by which Rifaximin-α influences MASLD progression.
Target Population: Patients diagnosed with MASLD. Intervention: This trial is a multicenter, prospective, randomized, controlled study. Enrolled MASLD patients who meet the inclusion criteria, do not meet any exclusion criteria, and provide written informed consent will be randomized in a 2:1 ratio to the Rifaximin-α treatment group (40 cases) or the control group (20 cases). All patients are advised to maintain daily physical activity and follow a recommended dietary plan (e.g., Mediterranean diet). The Rifaximin-α treatment group will receive oral Rifaximin-α at a dose of 1200 mg per day for 24 weeks. Both groups of patients will enter a 24-week follow-up period after completing the 24-week treatment. During the study, patients' existing foundational treatments (such as liver-protecting, lipid-lowering, glucose-lowering, and antihypertensive therapies) will be maintained. Relevant indicators will be closely monitored. And avoid the use of medications known to alter the gut microbiota, such as lactulose, antibiotics, and various types of intestinal microecological preparations.
Investigational Drug: Rifaximin-α (Alfa Wassermann S.p.A., Italy).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willingness to provide written informed consent.
- •Aged 18 to 75 years, inclusive, regardless of gender.
- •Diagnosis of hepatic steatosis (fatty liver) within the past 6 months.
- •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.
- •Liver fat content ≥ 8% as measured by Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF).
排除标准
- •Confirmed diagnosis of liver cirrhosis based on clinical, laboratory, imaging, and/or liver biopsy findings.
- •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.
- •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.
- •Use of medications known to alter gut microbiota (e.g., lactulose, systemic antibiotics, any intestinal microecological preparations) within 4 weeks prior to screening.
- •Dose of hepatoprotective or lipid-lowering medications not stabilized for at least 4 weeks prior to screening.
- •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.
- •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.
- •Self-reported weight change >5% within 4 weeks prior to screening.
- •BMI > 35 kg/m².
- •Poorly controlled glycemia: HbA1c > 9%.
- •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.
- •Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min/1.73 m².
- •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.
- •History of or current hepatocellular carcinoma (HCC).
- •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.
- •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.
- •HIV infection.
- •Known allergy or hypersensitivity to rifaximin.
- •Contraindications to MRI, such as incompatible metallic implants, claustrophobia, or body size exceeding scanner capacity.
- •Pregnant or lactating women, women of childbearing potential not using effective contraception, or individuals planning pregnancy.
- •Participation in another investigational drug trial within 3 months prior to screening.
- •Any other condition deemed by the investigator to be unsuitable for participation in the study.
研究组 & 干预措施
Control group
No Intervention
Patients are advised to maintain daily physical activity and follow a recommended dietary plan (e.g., Mediterranean diet).
Treatmnet group
Experimental
The Rifaximin treatment group will receive oral Rifaximin-α at a dose of 1200 mg per day for 24 weeks. And patients are advised to maintain daily physical activity and follow a recommended dietary plan (e.g., Mediterranean diet).
干预措施: Rifaximin-α (Alfa Wassermann S.p.A., Italy) (Drug)
结局指标
主要结局
The relative change in liver fat content measured by MRI from baseline to 24 weeks.
时间窗: From enrollment to the end of treatment at 24 weeks
The relative changes in MRI-measured liver proton density fat fraction (PDFF) at 24 weeks compared to baseline.
次要结局
- The absolute change in liver fat content measured by MRI from baseline to 24 weeks.(From enrollment to the end of treatment at 24 weeks)
- 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 12 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 12 weeks)
- Changes in serum alanine aminotransferase levels after 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in serum aspartate aminotransferase levels after 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in serum Gamma-Glutamyl Transferase levels after 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in serum Alkaline Phosphatase levels after 12 and 24 weeks of treatment compared to baseline(From enrollment to the end of treatment at 12 and 24 weeks)
- Change in liver fat content assessed via FibroScan after 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in fatty liver index (FLI) after 12 and 24 weeks of treatment compared to baseline.(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.(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.(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(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.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in FibroScan-AST (FAST) Score after 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in Body Mass Index (BMI) at 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in Waist circumference (WC) at 12 and 24 weeks of treatment compared to baseline.(From enrollment to the end of treatment at 12 and 24 weeks.)
- Changes in visceral adipose tissue (VAT) at 12 and 24 weeks of treatment compared to baseline. [(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in abdominal subcutaneous adipose tissue (ASAT) from baseline after 12 and 24 weeks of therapy(From enrollment to the end of treatment at 12 and 24 weeks)
- Changes in Cholesterol from baseline after 12 and 24 weeks of therapy.(From enrollment to the end of treatment at 12 and 24 weeks.)
- Changes in triglyceride from baseline after 12 and 24 weeks of therapy.(From enrollment to the end of treatment at 12 and 24 weeks.)
- Changes in Hemoglobin A1c (HbA1c) from baseline after 12 and 24 weeks of therapy.(From enrollment to the end of treatment at 12 and 24 weeks.)
- Changes in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) from baseline after 12 and 24 weeks of therapy.(From enrollment to the end of treatment at 12 and 24 weeks)
- The frequency and severity of treatment-related adverse events (AEs) as assessed by CTCAE 5.0.(From enrollment to the end of treatment at 24 weeks)
研究者
Wei-Fen Xie
Director, Department of Gastroenterology, Changzheng Hospital
Shanghai Changzheng Hospital
研究点 (1)
Loading locations...
相似试验
招募中
3 期
Study to Assess Rifaximin Soluble Solid Dispersion (SSD) for the Delay of Encephalopathy Decompensation in Cirrhosis (RED-C-3132)2022-502899-23-00Salix Pharmaceuticals Inc.194
招募中
4 期
Rifaximin 200 mg Plus Oral Rehydration vs Oral Rehydration Alone in Children With Acute DiarrheaGastroenteritisAcute DiarrheaBacterial InfectionNCT07285785Bausch Health Americas, Inc.54
招募中
1 期
Efficacy and Safety of Rifaximin in Treating MAFLDNCT07185932Shanghai Changzheng Hospital40
已完成
1 期
A Study to Assess the Pharmacokinetics of Rifaximin Soluble Solid Dispersion (SSD) Formulation in Adult Subjects with Impaired Hepatic Function2023-505434-98-00Salix Pharmaceuticals Inc.18
招募中
1 期
A Study of ABBV-295 Subcutaneous Injections to Assess Adverse Events and Pharmacokinetics in Adult Participants With ObesityObesityNCT07291232AbbVie80