The Microbiota Augmentation to Reestablish Commensal Organisms (MARCO) Trial

Description

The global burden of chronic liver disease (CLD) continues to rise. CLD is often clinically silent until an initial decompensation event, after which care is largely supportive without the ability to significantly modify the underlying disease with current therapies. Due to the high rates of infection in patients with liver disease, empiric, broad spectrum antibiotics are commonly prescribed. This practice is associated with altered gut microbiome compositions, reduced levels of health-promoting bacterial metabolites and high levels of antibiotic resistant organisms, findings that correlate with poor clinical outcomes including infection, repeat hepatic decompensation, re-hospitalization and death.

The primary objective of this clinical trial is to test the safety of commensal bacterial strain combinations designed to reconstitute microbiota compositions and metabolite production in patients with liver disease and profound dysbiosis as measured by low fecal metabolite (butyrate and deoxycholic acid) concentrations. The exploratory outcomes include strain engraftment and bacterial metabolite production.

The trial will occur in two phases. During the first phase, 8 patients will be recruited and administered the same combination of bacterial strains for 7 doses. Patients will be monitored for safety and tolerability. Additionally, fecal samples will be collected to assess for the presence of administered strains and fecal metabolite production.

After the first phase, additional combinations of bacteria will be chosen based upon the safety, engraftment and metabolite production in the first phase. In this adaptive phase, an additional 16 subjects will be enrolled and randomized to one of two additional consortia. In the two phases, a total of 24 patients will be enrolled, and each will be followed for 12 months to assess both primary (safety and tolerability) and exploratory (engraftment and metabolite production) outcomes. The investigators anticipate completing enrollment within 12 months of trial initiation.