Investigational Microbiota Restoration Therapeutic for Hepatic Encephalopathy

Phase 2

Terminated

• Conditions: Cirrhosis, Liver; Hepatic Encephalopathy
• Interventions: Biological: RBX7455; Biological: Placebo

• Registration Number: NCT04155099
• Lead Sponsor: Ochsner Health System

Brief Summary

Individuals with cirrhosis are likely to develop overt hepatic encephalopathy for which diagnostic modalities and treatment options are limited. The purpose of this study is to determine if individuals with cirrhosis who experience hepatic encephalopathy would benefit from investigational microbiota restoration therapy due to their inherent cognitive alterations. Analysis for a correlation between changes in microbiome composition and specific blood biomarkers could allow for earlier diagnosis of HE which could then be treated earlier and with novel treatments.

Detailed Description

The investigators hypothesize that changes in an individual's cognition due to HE-related liver cirrhosis can be stabilized and/or improved through investigational microbiota restoration therapeutic treatment. The main objective of this study is to determine if investigational microbiota restoration therapeutic treatment alters the cognitive function in individuals with cirrhosis who have been previously diagnosed with overt hepatic encephalopathy (HE). Once individuals have one HE episode, they are more likely to experience additional episodes, even after complying with standard of care. The number of HE episodes each study group experiences during the post-treatment follow-up will be compared among treatment groups. It is also anticipated that cognitive improvement will correlate with specific changes in the intestinal microbiota composition of these individuals likely shifting their microbiome away from baseline samples and becoming more like donor samples. Novel blood biomarkers potentially related to episodes of HE will be assessed in individuals before and after treatment.

Study Timeline

• Study First Submitted: 2019-08-21
• Study First Submitted QC: 2019-11-04
• Study First Posted: 2019-11-07
• Study Start: 2021-03-01
• Primary Completion: 2023-07-30
• Study Completion: 2023-07-30
• Status Verified: 2023-09
• Last Update Submitted: 2023-09-29
• Last Update Posted: 2023-10-03

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 5

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
High dose	RBX7455	Capsules of active drug will be supplied in 8-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.
pill quantity-matched Placebo	Placebo	Capsules of inactive compound will be supplied in 8- or 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.
Low dose	RBX7455	Capsules of active drug will be supplied in 4-capsule blister packets to be taken twice per week for four weeks. Blood and stool samples and cognitive assessments will be collected before treatment and at 1, 3, 6, and 12 months after treatment.

Primary Outcome Measures

Name	Time	Method
Change in cognitive function at 1 month post-FMT as measured by change in response times on EncephalApp (Stroop test)	1 month	Determine whether microbiota restoration therapy improves cognition 1 month after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement).; The scale for this measure is theoretically 0s-500s.

Secondary Outcome Measures

Name	Time	Method
Engraftment of FMT as assessed by change in type and abundance of gut microbiota following shotgun sequencing	1 month to 12 months	It is anticipated that with treatment, changes in the intestinal microbiota composition of these individuals will likely shift their microbiome to contain different species. Microbiome analyses will measure, at the family and genus level, which bacteria are present and their relative abundance. Samples from the same individual at different time points will be compared as well as differences between treatment groups at each time point.
Change in cognitive function at 3, 6 and 12 months post-FMT as measured by change in response times on EncephalApp (Stroop test)	3 to 12 months	Determine whether microbiota restoration therapy improves cognition 3, 6, and 12 months after treatment by measuring differences in time scores from EncephalApp. The app times participants in seconds (s) in variations of the Stroop Test. The average (s) across all trials will be reported as well as the difference in (s) between (trial 1)-(trial 5). Longer completion times indicate greater cognitive impairment, while a decrease in completion time from trial 1 to trial 5 indicates learning (cognitive improvement).
Number of HE episodes	1 month to 12 months	Once individuals have one HE episode, they are more likely to experience additional ones, even after complying with standard of care. The number of HE episodes each study group experiences during the post-treatment follow-up will be compared among treatment groups.

Trial Locations

Locations (1)

Ochsner Medical Center; 🇺🇸 Jefferson, Louisiana, United States