Fecal Microbiota Transplantation (FMT) in the Management of Hepatic Encephalopathy (HE): a Pilot Study

Study Overview
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Brief Summary
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The purpose of this study is to determine if FMT can reverse Hepatic Encephlopathy (HE) in cirrhotic patients who continue to have breakthrough episodes of HE despite maintenance therapy with lactulose and/or rifaximin or metronidazole.

Detailed Description
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Subjects receive FMT from a single donor by colonoscopy at Week 0 and by enema at Weeks 1-4. HE is measured by Inhibitory Control Test and Stroop as well as serum ammonia levels.

Official Title
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A Prospective, Single Center, Open Label Trial of Fecal Microbiota Transplantation (FMT) in the Management of Hepatic Encephalopathy (HE): a Pilot Study

Conditions
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Hepatic Encephalopathy

Intervention / Treatment
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* Biological: Fecal Microbiota Transplant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adult (age > 18 years of age) cirrhotic patients of various etiology, on lactulose and/or rifaximin or flagyl for at least 4 weeks as secondary prophylaxis abnormal inhibitory control test, defined as greater than 5 lures. an infectious etiology which may cause HE has been ruled out Exclusion Criteria: those with tense ascites those who do not provide assent those who are judged to have a life expectancy of less than 3 months, those who had TIPS within 3 months, those with neurologic diseases such as dementia, Parkinson's disease, and structural brain lesions pregnancy those with intestinal obstruction those with alcoholic hepatitis those with active alcohol or substance abuse those without stable social support those who have a concurrent infection, such as SBP, pneumonia or UTI those with creatinine clearance less than 50% compared to baseline those with recent hospital admission, defined as within one month of enrollment, for hepatic encephalopathy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fecal Microbiota Transplant<br>Single arm open label FMT administered at Week 0 by colonoscopy and at Weeks 1-4 by enema | Biological: Fecal Microbiota Transplant<br>* Fecal transplant processed from routinely screened universal donors<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Portion of participants with normailzation of ICT or Stroop Test during the study |  | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with normalization ICT or Stroop test scores at 1 week, 2 weeks, 4 weeks and 8 |  | 8 weeks | 
| Changes in serum ammonia level pre and post FMT |  | 8 weeks | 
| Changes in Quality of Life measured by Chronic Liver Disease Questionnaire (CDLQ) pre and post FMT |  | 8 weeks | 
| Changes in Intestinal Microbiota pre and post FMT |  | 8 weeks | 
| Serious Adverse Events | All serious adverse events up to and including week 8. A serious adverse event is any event which results in any of the following: i) Death ii) Colonic perforation iii) Proven infections as defined by the presence of i) spontaneous bacteremia: positive blood cultures in the absence of any other potential source of infection; ii) spontaneous bacterial peritonitis: ascetic fluid PMN equal to or greater than 250/mm3; iii) UTI: urinary leukocyte count greater than 15 cells per HPF and positive urine culture; vi) other infections identified by clinical, radiologic and bacteriologic results. iv) Possible infections as defined by i) fever (temp > 37.80 C), ii) leukocytosis (>15,000 mm3) or increased immature neutrophils in blood (>500 mm3), negative cultures and no other signs of infection. | 8 weeks | 
| Changes in stool bile acids composition pre and post FMT |  | 8 Weeks | 
| Changes in stool short chain fatty acids pre and post FMT |  | 8 weeks |