Fecal Microbiota Transplantation (FMT) in Nonalcoholic Steatohepatitis(NASH). A Pilot Study

Nonalcoholic Fatty Liver Disease Clinical Trial

Official title: Fecal Microbiota Transplantation (FMT) in Nonalcoholic Steatohepatitis(NASH). A Pilot Study

Status Recruiting

Clinical Trial Summary

Nonalcoholic steatohepatitis (NASH) is common, may progress to cirrhosis and is predicted to become a leading indication for liver transplantation in the near future. Though often associated with obesity and the metabolic syndrome, our current understanding of disease development is limited and there are few therapeutic options. Imbalance of gut bacteria is suspected to play a key role driving the progression of fatty liver disease and there is hope manipulation of these bacteria may be beneficial. This study will determine if fecal microbiota transplantation, using stool from lean donors, is an effective and safe treatment for NASH.

Clinical Trial Description

Nonalcoholic Steatohepatitis (NASH), a severe form of fatty liver disease, is highly prevalent and can lead to cirrhosis, liver failure and hepatocellular carcinoma. It is strongly associated with obesity and the metabolic syndrome. The impact of the gut microbiota on obesity and the metabolic syndrome is potentially large and increasing evidence suggests that dysbiosis might contribute to the development of NASH. There is a fundamental gap in understanding how alterations in the intestinal microbiota lead to a wide range of metabolic syndrome associated conditions including fatty liver disease in humans. The long-term goal of this project is to better understand the mechanisms linking intestinal dysbiosis and extra-intestinal clinical phenotypes, in particular obesity and NAFLD. Compositional shifts in gut bacteria from antibiotic use can perpetuate diseases such as Clostridum difficile infection, and manipulation of the microbiota through stool transplant from healthy donors can be used to cure disease. The objective of this application is to determine whether restoration of beneficial gut microbiota via fecal microbiota transplantation using stool from lean donors (FMT-L) improves NASH. The central hypothesis for this project is that transfer of gut microbiota from lean donors will result in reduced hepatic steatosis, and improved histological and biochemical features of NASH, all of which will correlate with observed changes in the small bowel and distal gut microbiome. This hypothesis will be tested by pursuing 3 specific aims: 1) determine the effect of FMT-L in patients with NASH on hepatic steatosis and markers of NASH; 2) perform microbiome analyses on pre- and post-FMT-L small bowel & stool samples; and 3) investigate mechanistic correlates linking dysbiosis with histologic changes in NASH after FMT-L. The study will be a pilot open labeled trial examining the effect of FMT-L in patients with biopsy proven NASH. The primary outcome measure will be a change in MRI-determined hepatic fat fraction,12 weeks after transplantation. Differences in the microbiota after FMT-L in the small bowel and distal gut, including the durability of microbiota changes, will be examined using advanced metagenomic techniques. Clinical and laboratory features of the metabolic syndrome and obesity as well as hepatic and systemic inflammatory markers will be examined for mechanistic correlates linking dysbiosis with histologic changes in the liver. In addition to understanding how the gut microbiota affects fatty liver disease progression, study findings will provide a framework for future microbiome research on metabolic syndrome related diseases such as diabetes, obesity, and other inflammatory disorders. An increased understanding of how the human gut microbiota is altered in metabolic disease may open a new avenue of therapeutics based on manipulation of gut bacteria. ;

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease

• NCT number: NCT02469272
• Study type: Interventional
• Source: Lifespan
• Contact: Robin Turnbull, RN
• Phone: 401-444-7344
• Email: rturnbull@lifespan.org
• Status: Recruiting
• Phase: Phase 1
• Start date: May 2015
• Completion date: June 2018