Fecal Transplant for Hepatic Encephalopathy

A Prospective Single Center Open Label Trial of RBX2660 (Microbiota Suspension) in the Management of Hepatic Encephalopathy

The purpose of the study is to determine if fecal microbiota transplant (FMT) can reverse hepatic encephalopathy (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: FMT

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 (ICT) and Stroop test as well as fasting serum ammonia levels.

• Study Type: Interventional
• Enrollment (Actual): 3
• 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 and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult cirrhotic patients of various etiology on lactulose and/pr rifaximin or metronidazole for minimum 4 weeks as secondary prophylaxis
• Abnormal ICT (>5 lures) or abnormal Stroop test (>200 seconds)
• Baseline Conn score 0 or 1
• Infectious etiology of HE has been ruled out

Exclusion Criteria:

• those with tense ascites
• those who do not provide assent
• life expectancy <3 months
• TIPS within the past 3 months
• neurologic disease such as dementia, Parkinson's, structural brain lesions
• pregnancy
• intestinal obstruction
• alcoholic hepatitis
• active alcohol or substance abuse
• those without stable social support
• concurrent infection such as spontaneous bacterial peritonitis, pneumonia or urinary tract infection
• creatinine clearance less that 50% compared to baseline
• hospital admission for HE within one month of enrollment
• active hepatocellular carcinoma
• active GI bleed

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: FMT; Open label FMT administered at week 0 by colonoscopy and weeks 1-4 by enema	Biological: FMT; FMT processed from routinely screened donors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Portion of participants with normalization 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	29 Questions Total- each question is on a seven point scales, ranging from the worst (1) to the best (7) possible function	8 weeks
Change in Intestinal Microbiota pre-and post FMT		8 weeks
Serious Adverse Events	i) 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
Change in stool Bile Acids Composition pre and post FMT		8 Weeks
Changes in stool short chain free fatty acids pre and post FMT		8 weeks

Collaborators and Investigators

• Sponsor: University of Alberta
• Collaborators: Rebiotix Inc.
• Investigators: Principal Investigator: Dina Kao, MD, Associate Professor

Study record dates

Study Major Dates

• Study Start (Actual): April 12, 2016
• Primary Completion (Actual): August 7, 2019
• Study Completion (Actual): March 18, 2021

Study Registration Dates

• First Submitted: February 13, 2018
• First Submitted That Met QC Criteria: February 13, 2018
• First Posted (Actual): February 20, 2018

Study Record Updates

• Last Update Posted (Actual): June 10, 2022
• Last Update Submitted That Met QC Criteria: June 7, 2022
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Hepatic encephalopathy, fecal microbiota transplant
• 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: Pro00060782

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No