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

Summary: 
      Randomized, open-label 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.
    

Detailed description: 
      Group 1 (FMT group) will undergo the following procedures

      Pre-FMT preparation:

      We will obtain written informed consent per the IRB guidelines. After the patients are
      consented and are eligible, we will perform a detailed medical history and physical exam at
      day 0. We will also perform cognitive testing. As in prior studies, we will prescribe
      patients an antibiotic regimen. Drawing from ecological principles of microbial niche
      environments and data from recurrent Clostridium difficile infection, pre-treatment
      antibiotics are likely to increase the probability of disrupting the hosts intrinsic
      microbiota and creating an opportunity for a 'healthy' microbiota from the FMT to engraft.

      After antibiotics and on the day of FMT:

      At day 5, we will re-evaluate patients with a directed interval history and focused physical
      exam as needed. After ensuring that they are still candidates according to the
      inclusion/exclusion criteria, we will collect stool, urine and blood again for pre-FMT
      evaluation and urine for pregnancy tests from eligible women. Cognitive testing will be
      performed again.

      Preparation and handling of stool for FMT infusion

      Standard protocol for handling bio-hazardous material will be employed in order to avoid
      contamination and risk to healthcare handlers. Sterile microbiological technique will be
      employed during material transfer peri-procedure.

      At that point we will provide the fecal material using universal precautions to a standard
      retention enema bag. The procedure will be completed by a trained Registered Nurse, Nurse
      practitioner, or physician in an outpatient clinic, endoscopy recovery area, or standard
      endoscopy unit.

      The following will be recorded in all FMTs

        -  Dose

        -  Unit ID/Lot# of each treatment

        -  Expiration Date

        -  Storage Condition

        -  FMT retention time (in minutes)

      Number of FMT: One administration Duration of Follow-up after FMT: 5 months

      Follow-up after FMT:

      We will see the patient in clinic the day following FMT (day 6 or FMT+1), day 12 (FMT+7), day
      20 (FMT+15), and day 35 (FMT+30), at which point a detailed history regarding abdominal
      symptoms, evaluation of infectious complications, hospitalizations or complications of
      cirrhosis.

      Visits on day 6, day 12 and day 35 will be purely safety associated while, on the day 20
      visit, we will repeat the pathophysiological studies.

      In order to ensure that we have enough samples, in case patients are not able to return at
      day 20, we will also collect all samples at day 12, but will only analyze them in case the
      day 20 visit does not occur.

      These visits, apart from the visit after FMT, will be ±2 days for patient convenience.

      At 5 months post-FMT, subjects will be followed up with a phone call to evaluate potential
      SAEs, new onset of transmitted infections, new onset or significant worsening of chronic
      medical conditions or suspected unexpected serious adverse reactions that have occurred in
      between 35 days and 5 months for reporting purposes.

      Samples collected at baseline (before FMT), after antibiotics and at day 15 will be:

        1. Stool

        2. Blood

        3. Urine

      Group 2: No treatment arm The group 2 will undergo all sample collections, follow-up and
      cognitive testing as in group 1 but without the 5-day antibiotic therapy or the FMT. In
      addition, we will also not perform the sample collection that is done after 5 days of
      antibiotics in this group since no reasonable change in microbiota are expected over 5 days
      without antibiotics. The follow-up of this group will be same as that of the FMT group.
    

Intervention name(s): Fecal transplant
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: hepatic encephalopathy; fecal transplant; cirrhosis