The Effect of Consecutive Fecal Microbiota Transplantation on Non-Alcoholic Fatty Liver Disease (NAFLD) - a Randomized-controlled Trial -
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 20
- 试验地点
- 2
- 主要终点
- the effect on consecutive FMT on liver fat accumulation
研究概览
简要总结
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The primary objective is to study the effect of consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are weight, waist, blood pressure, metabolic parameters (including glucose, cholesterol, pancreatic beta-cell function, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition and liver enzymes. Stool samples will be collected for microbiota analysis at time point 0, 3, 6 and 12 weeks.
详细描述
Nonalcoholic fatty liver disease (NAFLD) is a disease of alarmingly increasing prevalence, linked to metabolic, cardiovascular and malignant morbidity and without any officially approved treatment. It is increasingly recognized that the gut microbiome is implicated in the pathogenesis and progression of numerous chronic diseases, including NAFLD. Through the so-called gut-liver axis, the liver is exposed to gut-bacterial-derived products, including toxins (lipopolysaccharides), enzymes (methylamines), alcohol, and short-chain fatty acids (mainly acetate, propionate, and butyrate), that may lead to accumulation of triglycerides, inflammatory responses, oxidative stress and accompanying damage to the hepatocytes. The investigators hypothesize that altered gut microbiota underlie (hepatic) insulin resistance and liver fat accumulation in NAFLD patients. Fecal microbiota transplantation, through amelioration of gut-microbiota released products like lipopolysaccharides, short-chain fatty acids, alcohol and enzymes, and changes in bile acids, may positively affect NAFLD.
During the study 20 patients will be randomized for infusion of allogenic (lean donor) or autologous (own) feces by gastroscopy at time points 0, 3 and 6 weeks on a 1:1 basis. Prior to randomization, and at 12 weeks, all patients will undergo LiverMultiscan to non-invasively quantify liver fat accumulation and other features of NAFLD. In addition, various metabolic parameters (lipids, HOMA-IR), objective and subjective stress indicators, gut-microbiota and bile composition, and liver enzymes will be measured.
The primary objective is to study the effect on consecutive FMT on liver fat accumulation measured by Magnetic Resonance Images (MRI) LiverMultiscan at 12 weeks. Secondary objectives are alterations in anthropometrical data (weight, waist, blood pressure), changes in fecal microbiota, liver enzymes, bile composition and metabolic parameters including glucose, lipids, pancreatic beta-cell function and insulin resistance measured as HOMA-IR and objective and subjective stress indicators.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Double-blinded RCT, randomization by Dutch Donor Feces Bank
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Obese (BMI > 27 kg/m2)
- •Males and postmenopausal females
- •Aged 18 to 70 years
- •Hepatic steatosis defined as increased hyperechogenicity of the liver on abdominal ultrasound and/or histological signs of steatosis
- •Written informed consent
排除标准
- •Exclusion criteria for MRI (claustrophobia, pacemaker, metal implants, etc)
- •Any other liver disease than NAFLD/NASH
- •Present excessive alcohol use defined as > 2 units/day
- •Recent use (< 3 months) of antibiotics
- •use of possible drugs interfering microbiota or recent (< 3 months) changes in dosages
- •use of GLP-1 RA or SU-derivatives
- •Recent (< 3 months) weight change (>5%)
- •Cardiovascular co-morbidity defined as heart failure, coronary insufficiency and hypertension in past history
- •Previous use of glucocorticosteroids, hormonal substitution, pagitaxel, theofyllin, amiodarone, myelosuppresive agents.
- •A psychiatric, addictive or any other disorder that compromises the subjects ability to understand the study content and to give written informed consent for participation in the study
结局指标
主要结局
the effect on consecutive FMT on liver fat accumulation
时间窗: 12 weeks
measured by MRI Livermultiscan
次要结局
- alterations in liver enzymes(3, 6 and 12 weeks)
- changes in lipid homeostasis(3, 6 and 12 weeks)
- alterations in psychological stress(0 and 12 weeks)
- change in bile composition(3 and 6 weeks)
- change in bacterial species in small intestine and feces(3 and 6 weeks)
- alterations in anthropometric data(3, 6 and 12 weeks)
- alterations in pancreatic beta-cell function and insulin resistance(3, 6 and 12 weeks)
- changes in physical activity(during 14 weeks)
研究者
metushuizen
Principle investigator
Leiden University Medical Center