Fecal Microbial Transplant for Alcohol Misuse in Cirrhosis
Condition: Cirrhosis; Alcohol Abuse
MeSH terms: Liver Cirrhosis; Fibrosis; Alcoholism
Study type: Interventional
Phase: Phase 1

Summary: 
      There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans
      all ages and socio-economic strata, which has a major impact on healthcare expenditure.
      Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease
      including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most
      patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are
      not willing to quit drinking. These patients are neither liver transplant candidates due to
      their drinking nor have any recourse to therapies directed towards the liver as is the case
      with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have
      many therapeutic options.

      Prior studies have demonstrated that these patients have an altered gut-liver axis which is
      exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids.
      These secondary bile acids in turn have the potential to worsen the already impaired gut
      barrier in these patients, creating a vicious cycle of inflammation and further liver injury
      that is led by the altered microbial composition. A gut-based strategy that has the
      capability of "resetting" this dysbiosis could help in the amelioration of this inflammatory
      load and improve the prognosis of these patients.
    

Detailed description: 
      Randomized, single-blind, placebo-controlled safety, tolerability study with exploratory
      endpoints and pathophysiological evaluation of the FMT

      Two groups of outpatients with cirrhosis will be randomized using random sequence generator
      into no-treatment and FMT groups.

      Once patients are randomized 1:1 into group 1 (FMT) and group 2 (Placebo), both will be
      followed over 31 days and will include a 6 month visit to collect samples, perform
      questionnaires and to assess SAEs.

      There is an epidemic of alcohol use disorder in the US. Alcoholism is an epidemic that spans
      all ages and socio-economic strata, which has a major impact on healthcare expenditure.
      Alcohol-associated liver disease can take the form of mild fatty liver, chronic liver disease
      including cirrhosis and a very acute active form known as alcoholic hepatitis. However, most
      patients with alcohol abuse issues with cirrhosis do not develop alcoholic hepatitis and are
      not willing to quit drinking. These patients are neither liver transplant candidates due to
      their drinking nor have any recourse to therapies directed towards the liver as is the case
      with alcoholic hepatitis. This is very large proportion of cirrhotic patients who do not have
      many therapeutic options.

      Prior studies have demonstrated that these patients have an altered gut-liver axis which is
      exacerbated by dysbiosis and a higher production of potentially toxic secondary bile acids.
      These secondary bile acids in turn have the potential to worsen the already impaired gut
      barrier in these patients, creating a vicious cycle of inflammation and further liver injury
      that is led by the altered microbial composition. The investigators believe that a gut-based
      strategy that has the capability of "resetting" this dysbiosis can help in the amelioration
      of this inflammatory load and improve the prognosis of these patients.
    

Intervention name(s): Fecal Microbial Transplant; Placebo
Intervention type(s): Biological; Other
Intervention description(s): Fecal transplant from a donor in the OpenBiome Registry; Placebo enemas
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment