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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatic Encephalopathy
• Intervention / Treatment: Biological: Fecal Microbiota Transplant

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. abnormal inhibitory control test, defined as greater than 5 lures.
3. an infectious etiology which may cause HE has been ruled out

Exclusion Criteria:

1. those with tense ascites
2. those who do not provide assent
3. those who are judged to have a life expectancy of less than 3 months,
4. those who had TIPS within 3 months,
5. those with neurologic diseases such as dementia, Parkinson's disease, and structural brain lesions
6. pregnancy
7. those with intestinal obstruction
8. those with alcoholic hepatitis
9. those with active alcohol or substance abuse
10. those without stable social support
11. those who have a concurrent infection, such as SBP, pneumonia or UTI
12. those with creatinine clearance less than 50% compared to baseline
13. those with recent hospital admission, defined as within one month of enrollment, for hepatic encephalopathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of Alberta

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2014
• Primary Completion (Actual): July 25, 2019
• Study Completion (Actual): September 23, 2019

Study Registration Dates

• First Submitted: August 26, 2014
• First Submitted That Met QC Criteria: September 29, 2014
• First Posted (Estimate): October 2, 2014

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Liver Diseases; Brain Diseases, Metabolic; Hepatic Encephalopathy; Brain Diseases
• Other Study ID Numbers: 47057