Oral Fecal Transplant in Cirrhosis
Condition: Hepatic Encephalopathy; Cirrhosis, Liver
MeSH terms: Liver Cirrhosis; Hepatic Encephalopathy; Brain Diseases; Fibrosis
Study type: Interventional
Phase: Phase 1

Summary: 
      To evaluate the safety and tolerability of oral fecal transplant in patients with cirrhosis
      and hepatic encephalopathy
    

Detailed description: 
      Hepatic encephalopathy affects 30-45% of patients with cirrhosis and adversely affects
      survival in these patients. The mainstay of treatment for hepatic encephalopathy (HE) has
      long been the manipulation of the gut microbiota through antibiotics, prebiotics or
      probiotics. The current first and second line therapies for HE in the US are lactulose and
      rifaximin respectively that uniquely act within the confines of the gut lumen with
      encouraging clinical results. However there is a subset of patients with HE that continues to
      recur despite being on both treatments. This patient group is at a higher risk of poor
      outcomes because HE has now been removed from liver transplant priority and multiple episodes
      of HE can result in cumulative brain injury which may be irreversible. Therefore the
      prevention of recurrent HE is an important therapeutic goal.

      The study team's research and other reports have shown that patients with HE and cirrhosis
      are more likely to have overgrowth of potentially pathogenic bacterial taxa such as
      Enterobacteriaceae and reduction of autochthonous species such as Lachnospiraceae and
      Ruminococcaceae in the stool and the colonic mucosa. This has been linked to poor performance
      on cognitive tests that are a hallmark of HE and with increased systemic inflammation in
      these patients.

      Therefore a gut-based therapeutic option that can potentially improve the recurrence rate and
      the overall prognosis is needed. Fecal transplant has been shown to be effective in
      conditions with predominant gut-bacterial overgrowth or alteration such as recurrent
      Clostridium difficile and inflammatory bowel disease. Safe protocols have been developed
      across the world and studies are being performed in the US under FDA-monitored INDs.
      Limitations to performing fecal transplant include identifying and screening appropriate
      donors, which is time consuming and costly, with the cost typically falling to the patient or
      donor as the required screening is generally not covered by insurance. For this reason, the
      study team is particularly interested in working with Openbiome and have obtained their
      collaboration towards performing this Fecal Microbiota Transplantation (FMT) by
      cross-referencing of their drug master file.

      The preliminary data suggest that a one-time administration of an FMT-enema using a
      rationally-selected donor via Openbiome is safe in patients with cirrhosis and recurrent HE.
      However, given the small bowel overgrowth and the predominantly small bowel location for
      bacterial translocation in cirrhosis, which is out of the reach of an enema, an upper GI
      route for FMT needs to be explored. The FMT capsule by Openbiome acts on the small and large
      intestine and is available for C.difficile. It is potentially more acceptable to patients for
      repeated administrations and in cirrhosis has the advantage of acting on the small bowel in
      addition to the large bowel. The study will use a donor specifically selected from the
      Openbiome pool whose microbial profile best fulfils the microbiota deficits related to
      beneficial bacteria in HE patients, utilizing a "Precision Microbiome" approach.
    

Intervention name(s): FMT; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Fifteen FMT Openbiome capsules administered at the same time; Fifteen placebo capsules administered at the same time
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Placebo-controlled single-blind randomized trial
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Hepatic Encephalopathy; Cirrhosis; Liver; Openbiome; FMT Capsule; Placebo