Synbiotics and Fecal Microbiota Transplantation to Treat Non-Alcoholic Steatohepatitis
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 48
- 试验地点
- 2
- 主要终点
- Liver histology
研究概览
简要总结
The goal of this clinical trial is to investigate the therapeutic potential of A. soehngenii and pasteurized A. muciniphila combined with B. animalis subsp. lactis and fructo-oligosaccharides with and without conditioned vegan lyophilized fecal microbiota transplantation capsules to reduce NASH in patients with fibrotic NASH. The main questions to answer are:
- Can NASH be treated by altering the gut microbiota using LFMT capsules?
- Can NASH be treated using a syntrophic cocktail of synbiotics and will these strains strengthen the effect of FMT?
- What are the underlying mechanism by which the aforementioned treatments attenuate NASH?
Participants will be treated with FMT-capsules or placebo, and all participants will receive a cocktail of 3 strains of probiotics and one type of prebiotic.
详细描述
Main objective To investigate the therapeutic potential of A. soehngenii and pasteurized A. muciniphila combined with B. animalis subsp. lactis and fructo-oligosaccharides with and without conditioned vegan lyophilized fecal microbiota transplantation (LFMT) capsules to reduce NASH in patients with NASH and NASH-fibrosis.
Secondary objective To investigate the mechanisms of A. soehngenii and pasteurized A. muciniphila combined with B. animalis subsp. lactis and FOS with and without conditioned vegan LFMT capsules in reducing NASH in patients with NASH and NASH-fibrosis.
Study design:
Double-blind randomized placebo-controlled intervention study.
Study population:
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
Doubleblind
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
- •biopsy-proven NASH obtained up to 32 weeks before screening: SAF Steatosis score ≥1, Activity ≥2, Fibrosis <4; 50% of participants should at least have NASH fibrosis stage 1, 2 or 3 according to the NASH CRN fibrosis staging system based on tandem reading of two expert liver pathologists
- •fluency in Dutch or English
- •participants should be able to understand the information and give informed consent
排除标准
- •Current or history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year before screening (significant alcohol consumption is defined as more than 2 international units/day for females and more than 3 international units/day for males, on average; 1 international unit contains ±14 grams of alcohol)
- •liver cirrhosis or hepatocellular carcinoma
- •hepatitis B and/or C
- •auto-immune hepatitis
- •Wilson's disease
- •primary sclerosing cholangitis
- •primary biliary cholangitis
- •alpha-1-antitripsine deficiency and hemochromatosis
- •history of liver transplant, current placement on a liver transplant list
- •use of pre-, pro- or synbiotics
- •use of systemic antibiotics 3 month prior to randomization
- •use of tamoxifen, methotrexate or amiodarone
- •prior or planned bariatric surgery
- •active GLP-1 receptor agonist treated diabetes mellitus
- •bleeding disorder
- •International normalized ratio (INR) of prothrombin time >1.4 or platelet count <100 109/L at screening
- •anti-platelet/coagulant therapy use which cannot be temporarily discontinued
- •any major cardiovascular event within 6 months prior to screening (e.g. myocardial infarction, cerebrovascular accident)
- •prolonged compromised immunity (e.g. recent cytotoxic chemotherapy, HIV-infection with a CD4 count < 240)
- •active or prior history of invasive malignancy (except for curatively treated in situ carcinomas [e.g., cervix] or non-melanoma skin cancer) unless a complete remission was achieved
- •surgery scheduled for the trial duration period, except for minor surgical procedures, in the opinion of the investigator
- •pregnant or nursing women
- •any condition which, in the investigator's opinion, might jeopardize participants' safety or compliance with the protocol
- •participation in another concomitant clinical trial.
结局指标
主要结局
Liver histology
时间窗: baseline and after 24 weeks
Alteration of liver histology in subjects with NASH and fibrosis stage 0-3, with an alteration defined as change of steatohepatitis by ≥1 SAF-A point, or a change in ≥ 1 stage liver fibrosis.
次要结局
- Fibroscan(baseline and after 24 weeks)
- Liver enzymes (blood)(baseline and after 24 weeks; 8 and 16 weeks for safety.)
- MRI(baseline and after 24 weeks)
- Gut metabolites (in blood)(baseline and after 24 weeks)
- NAFLD NASH related endocrinological and metabolic outcome parameters(Baseline and 24 weeks)
- Microbiome readouts(baseline and after 24 weeks, and 5 times in between.)
- Immunological data(baseline and after 24 weeks)
- Plasma lipids(baseline and after 24 weeks)
- Glycemic control(5 weeks during study period)
- BMI(baseline and after 24 weeks)
- Height(baseline)
- albumin, kreatinine, hemoglobin (blood)(baseline, 8, 16 and 24 weeks)
- Body weight(baseline and after 24 weeks)
- Waist circumference(baseline and after 24 weeks)
- Percentage body fat(baseline and after 24 weeks)
- Demographics and (medical) history(baseline and 24 weeks)
- Quality of life with CDLQ-NASH(baseline and after 24 weeks)
- Quality of life with SF36 questionnaire.(baseline and after 24 weeks)
- Food diary(around the visits 0, 8, 16, 24 weeks)
研究者
Onno Holleboom, MD, PhD
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)