A Single-Arm, Proof-of-Concept Study of Dihydroartemisinin in Adults With Metabolic Associated Fatty Liver Disease
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in Liver Fat Content Measured by MRI Proton Density Fat Fraction (MRI-PDFF)
研究概览
简要总结
Brief Summary
Purpose:
This is a proof-of-concept clinical trial to evaluate whether Dihydroartemisinin (DHA), a medication commonly used to treat malaria, can effectively reduce liver fat in adults with Metabolic Associated Fatty Liver Disease (MAFLD). The study will also rigorously assess the safety and tolerability of DHA in this specific patient population.
Study Design:
This is a single-center, open-label, single-arm study. All qualified participants will receive the investigational treatment, with each individual serving as their own baseline control to measure pre- and post-treatment changes. To minimize lifestyle-related confounding factors, all participants will receive standardized dietary and physical activity counseling at baseline and will be instructed to strictly maintain their established lifestyle routines throughout the study period.
Participants:
The study plans to enroll approximately 30 adult patients (ages 18 to 45 years) formally diagnosed with MAFLD. MAFLD is defined by the presence of excessive hepatic fat accumulation concurrent with specific metabolic dysfunctions, such as overweight/obesity, hypertension, elevated blood sugar, or dyslipidemia.
Intervention:
Participants will be administered oral Dihydroartemisinin tablets at a dose of 20 mg three times daily (TID) for a continuous duration of 12 weeks. Upon completion of the intervention, participants will enter a 12-week observational follow-up period to monitor the durability of the treatment effects and long-term safety.
Main Things We Will Measure (Outcomes):
Primary Outcome: Absolute change in liver fat content from baseline to the end of the 12-week treatment, quantitatively assessed by the gold-standard MRI Proton Density Fat Fraction (MRI-PDFF).
Secondary Outcomes: Changes in supplementary non-invasive liver fat assessments (including Ultrasound-derived Fat Fraction [UDFF] and FibroScan Controlled Attenuation Parameter [CAP]), as well as changes in body weight, blood pressure, heart rate, and routine laboratory safety panels (e.g., comprehensive liver and kidney function tests).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Aged 18-45 years (inclusive), any gender.
- •Meets the diagnostic criteria for Metabolic Associated Fatty Liver Disease (MAFLD), requiring both of the following:
- •Evidence of hepatic steatosis (at least one of the following):
- •Imaging: Ultrasound, CT, or MRI-PDFF showing liver fat content ≥5%.
- •Liver biopsy: Histologically confirmed steatosis ≥5% (within 6 months prior to enrollment).
- •FibroScan: Controlled Attenuation Parameter (CAP) ≥248 dB/m.
- •Evidence of metabolic dysfunction (at least one of the following):
- •Overweight/Obesity: BMI ≥24 kg/m² or waist circumference ≥90 cm (male) / ≥85 cm (female).
- •Elevated blood pressure/Hypertension: Blood pressure ≥130/85 mmHg, or on antihypertensive medication.
- •Pre-diabetes or Type 2 Diabetes: Fasting blood glucose ≥6.1 mmol/L, or 2-hour post-load glucose ≥7.8 mmol/L, or HbA1c ≥5.7%, or history of T2DM, or HOMA-IR ≥2.
- •Elevated blood triglycerides: Fasting serum TG ≥1.70 mmol/L, or on lipid-lowering medication.
- •Reduced HDL-cholesterol: Serum HDL ≤1.0 mmol/L (male) / ≤1.3 mmol/L (female), or on lipid-lowering medication.
- •Participants on glucose-, blood pressure-, or lipid-lowering medications must have been on a stable dose for at least 3 months prior to screening.
- •All participants must have stable body weight (defined as weight loss or gain not exceeding 5% within 3 months prior to screening and from screening to enrollment).
- •Voluntary participation, willingness to cooperate with follow-up, and signed informed consent.
排除标准
- •Liver function impairment (defined as any one of ALT, AST, GGT, ALP exceeding 2 times the upper limit of normal (ULN) and/or bilirubin exceeding 1.5 times ULN).
- •Long-term use (exceeding 2 weeks) of drugs known to cause hepatic steatosis or fibrosis (e.g., glucocorticoids, valproate, methotrexate, tamoxifen, amiodarone, oral vitamin E) within the past year.
- •Excessive alcohol consumption: weekly ethanol intake ≥210 g (male) or ≥140 g (female).
- •Positive for Hepatitis B surface antigen (HBsAg) or Hepatitis C virus antibody (HCV-Ab).
- •Specific liver diseases that can cause fatty liver (e.g., autoimmune hepatitis, Wilson's disease) or other specific conditions (e.g., total parenteral nutrition, inflammatory bowel disease, celiac disease, hypothyroidism, Cushing's syndrome, abetalipoproteinemia, lipodystrophic diabetes, Mauriac syndrome).
- •History of leukopenia or agranulocytosis.
- •History of bariatric surgery within the past 2 years.
- •Pregnant, planning pregnancy, or lactating women.
- •History of malignancy, cardiovascular disease, chronic kidney disease, decompensated cirrhosis (e.g., ascites, variceal bleeding, hepatic encephalopathy, hepatorenal syndrome), or liver transplantation.
- •Use of any category of antibiotics within 2 weeks prior to enrollment.
- •Considered by the clinical investigator to be unsuitable for participation in the study.
结局指标
主要结局
Change in Liver Fat Content Measured by MRI Proton Density Fat Fraction (MRI-PDFF)
时间窗: Baseline (Week 0) to End of Treatment (Week 12)
Absolute change in liver fat percentage (%) from baseline to the end of treatment, as assessed by MRI-PDFF
次要结局
- Change in Controlled Attenuation Parameter (CAP)(Baseline (Week 0), End of Treatment (Week 12), End of Follow-up (Week 24))
- Change in Liver Fat Content Measured by Ultrasound-derived Fat Fraction (UDFF)(Baseline (Week 0) to End of Treatment (Week 12))
- Change in Body Weight(Baseline (Week 0), End of Treatment (Week 12), End of Follow-up (Week 24))
研究者
Xuehao Wang
Professor
The First Affiliated Hospital with Nanjing Medical University