Efficacy and Safety of E.Coli Nissle 1917 in Patients With Mild (Stage 1-2) or Minimal Hepatic Encephalopathy

Probiotic E.Coli Nissle 1917 Comparing to Lactulose and Rifaximin in Patients With Mild (Stage 1-2) or Minimal Hepatic Encephalopathy

The purpose of study to assess the short-term efficacy and safety of probiotic E.coli Nissle 1917 strain comparing to lactulose and rifaximin in patients with mild (Stage 1-2) or minimal hepatic encephalopathy

Study Overview

• Status: Completed
• Conditions: Liver Cirrhosis; Hepatic Encephalopathy; End Stage Liver DIsease
• Intervention / Treatment: Dietary supplement: E.coli Nissle 1917; Drug: Lactulose; Drug: Rifaximin

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Not Applicable

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:

• Cirrhosis diagnosed on the basis of liver biopsy, liver stiffness measurement or radiological study;
• presence of minimal or mild (Grade 1-2) HE as defined by West Haven criteria;
• two or more documented episodes of HE in the last 6 months, in addition to at least one episode in the last 3 months;
• subject is capable and willing to comply with all study procedures;
• signed inform consent.

Exclusion Criteria:

• history of taking L-ornithine- L -aspartate, zinc, metronidazole, or neomycin, antibiotics, probiotics and yogurt consumption within 6 weeks;
• subject has a history of allergy or intolerance to lactulose and/or rifaximin;
• alcohol intake during the past 6 month or during follow up;
• recent (6 weeks) gastro-intestinal bleed;
• hepato-cellular carcinoma or liver transplantation;
• renal insufficiency;
• significant comorbid illness such as heart or respiratory failure;
• concurrent infection such as spontaneous bacterial peritonitis, pneumonia or urinary tract infection;
• any neurologic diseases such as alzheimer's disease, parkinson's disease and nonhepatic metabolic encephalopathies;
• subject has any condition or circumstance that would, in the opinion of the Investigator, prevent completion of the study or interfere with analysis of study results, including history of noncompliance with treatments.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: E.coli Nissle 1917; probiotic, oral, for the first 4 days, 1 capsule, and then 2 capsules per day for 1 month treatment	Dietary supplement: E.coli Nissle 1917; Probiotic contains biomass of E.coli Nissle 1917, 2,5-25·109 colony forming units - CFU/g; Other Names: MUTAFLOR capsules
ACTIVE_COMPARATOR: Lactulose; will receive 30-60 ml of lactulose in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day, 1 months of treatment	Drug: Lactulose; will receive 30-60 ml of lactulose in 2 or 3 divided doses so that patient passed 2-3 semisoft stools per day, 1 months of treatment; Other Names: DUPHALAC
ACTIVE_COMPARATOR: Rifaximin; rifaximin, oral, 500 mg BID, 1 months of treatment	Drug: Rifaximin; rifaximin, oral, 500 mg BID, 1 months of treatment; Other Names: Alfa Normix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Stroop test	1 month
Change in serum ammonia	1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in serum inflammatory cytokine	The level of IL-6, IL-8 and INFγ in pg / ml will be assesed	1 month
Bacteriology measured in the stool flora by specialized non-culture techniques	The percentage of patients in each group were evaluated and characterized by a decrease below the normal content of symbiotic bacteria Bifidobacterium (less than 107 CFU / g), lactobacilli (less than 107 CFU / d), E.coli with normal properties (less than 106 CFU / d) and increase in content E.coli with altered properties (more than 106 CFU / g), pathogenic enterobacteria (not normally detected) and fungi of the genus Candida (more than 104 CFU / d)	1 month

Collaborators and Investigators

• Sponsor: Bogomolets National Medical University
• Investigators: Principal Investigator: Elina Manzhalii, PhD, Bogomolets National Medical University

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 10, 2017
• Primary Completion (ACTUAL): January 15, 2020
• Study Completion (ACTUAL): March 15, 2020

Study Registration Dates

• First Submitted: March 2, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (ACTUAL): March 8, 2021

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Liver Cirrhosis; hepatic encephalopathy; Probiotic; rifaximin; lactulose; End Stage Liver DIsease; E.coli Nissle 1917
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Failure; Hepatic Insufficiency; Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Diseases, Metabolic; Liver Diseases; End Stage Liver Disease; Fibrosis; Liver Cirrhosis; Hepatic Encephalopathy; Brain Diseases; Anti-Infective Agents; Gastrointestinal Agents; Anti-Bacterial Agents; Rifaximin; Lactulose
• Other Study ID Numbers: HepEN

Drug and device information, study documents

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