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

Phase 1

Completed

• Conditions: Hepatic Encephalopathy
• Interventions: Biological: Fecal Microbiota Transplant

• Registration Number: NCT02255617
• Lead Sponsor: University of Alberta

Brief Summary

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

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 Timeline

• Study Start: 2014-07-23
• Study First Submitted: 2014-08-26
• Study First Submitted QC: 2014-09-29
• Study First Posted: 2014-10-02
• Primary Completion: 2019-07-25
• Study Completion: 2019-09-23
• Status Verified: 2021-09
• Last Update Submitted: 2021-09-27
• Last Update Posted: 2021-10-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 4

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Fecal Microbiota Transplant	Fecal Microbiota Transplant	Single arm open label FMT administered at Week 0 by colonoscopy and at Weeks 1-4 by enema

Primary Outcome Measures

Name	Time	Method
Portion of participants with normailzation of ICT or Stroop Test during the study	8 weeks

Secondary Outcome Measures

Name	Time	Method
Changes in serum ammonia level pre and post FMT	8 weeks
Changes in Intestinal Microbiota pre and post FMT	8 weeks
Proportion of patients with normalization ICT or Stroop test scores at 1 week, 2 weeks, 4 weeks and 8	8 weeks
Changes in Quality of Life measured by Chronic Liver Disease Questionnaire (CDLQ) pre and post FMT	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
Serious Adverse Events	8 weeks	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.

Trial Locations

Locations (1)

University of Alberta Hospital; 🇨🇦 Edmonton, Alberta, Canada