Fecal Transplant in Recurrent Hepatic Encephalopathy
Safety and Tolerability of Fecal Microbiota Transplantation in Cirrhosis and Hepatic Encephalopathy
  • Phase

    Phase 1
  • Study Type

  • Status

    Completed No Results Posted
  • Study Participants

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.
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

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:


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.
Study Started
Oct 31
Primary Completion
Aug 31
Study Completion
Aug 31
Last Update
Jul 05

FMT Active Comparator

Fecal transplant via enema once

No treatment No Intervention

No transplant performed


Inclusion Criteria:

Cirrhosis diagnosed by either of the following in a patient with chronic liver disease

Liver Biopsy
Radiologic evidence of varices, cirrhosis or portal hypertension
Laboratory evidence of platelet count <100,000 or AST/ALT ratio>1
Endoscopic evidence of varices or portal gastropathy
At least two episodes of hepatic encephalopathy, one within the last year but not within the last month (patient can be on lactulose and rifaximin)
Age between 21 and 75
Able to give written, informed consent (demonstrated by mini-mental status exam>25 at the time of consenting)

Exclusion Criteria:

MELD score >17
WBC count <1000 cells/mm3
Platelet count<50,000/mm3
On the liver transplant list
TIPS in place
No HE episode within a month prior to the study
Patients allergic to ciprofloxacin, penicillins or metronidazole
Currently on absorbable antibiotics
Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed)
Hospitalization for any non-elective cause within the last 3 months
Patients who are aged >75 years
Patients who are pregnant or nursing (will be checked using a urine pregnancy test)
Patients who are incarcerated
Patients who are incapable of giving their own informed consent

Patients who are immuno-compromised due to the following reasons:

HIV infection (any CD4 count)
Inherited/primary immune disorders
Current or recent (<3 mos) treatment with anti-neoplastic agent
Current or recent (<3 mos) treatment with any immunosuppressant medications [including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil]. Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll.
Patients with a history of severe (anaphylactic) food allergy
Patients who have previously undergone FMT
Patients on renal replacement therapy
Patients who are unwilling or unable to hold the enemas
Patients with untreated, in-situ colorectal cancer
Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease (ulcerative colitis, Crohn's disease or microscopic colitis) , eosinophilic gastroenteritis, celiac disease or irritable bowel syndrome
Major gastro-intestinal or intra-abdominal surgery in the last three months
Unable to comply with protocol requirements
Patients who are American Society of Anesthesiologists (ASA) Physical Status classification IV and V
Patients with acute illness or fever on the day of planned FMT will be excluded with the option of including that subject at a future date
Any conditions for which, in opinion of MD, the treatment may pose a health risk
C. difficile in the stool at baseline (qPCR)
Grade 2-4 or complicated hemorrhoids
No Results Posted