VE303 for Treatment of Hepatic Encephalopathy (HE)

Phase 2

Completed

Conditions: Cirrhosis
Hepatic Encephalopathy

Interventions: Drug: Placebo
Drug: VE303
Drug: oral vancomycin

Registration Number: NCT04899115

Lead Sponsor: Patricia Bloom

Brief Summary: This research is studying the use of a new drug to learn about its safety and efficacy as a treatment for hepatic encephalopathy.

Eligible participants will be enrolled and given oral antibiotics followed by 14 days of the study drug (placebo vs.VE303). There will be visits as well as other procedures to collect blood and stool samples, and have tests of your cognition (thinking) for this research study.

The hypothesis is that VE303 will safely and effectively improve cognitive function in patients with a history of overt hepatic encephalopathy.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

Inclusion Criteria

Diagnosis of cirrhosis based on liver biopsy, imaging, or evidence of clinical decompensation
History of at least one episode of overt HE any time in the past
Prescribed both lactulose and rifaximin, and compliant with this treatment

Exclusion Criteria

Current episode of overt HE
Variceal bleeding in the last 4 weeks
Gut-absorbable or intravenous antibiotic therapy in the last 28 days
Fecal microbiota transplant in the last 6 months
Use of probiotics in the last 2 weeks
Alcohol or illicit drug intake in the last 4 weeks
Primary sclerosing cholangitis as etiology of liver disease
History of inflammatory bowel disease, short gut, gastrointestinal tract fistulas, intestinal ischemia, or any form of ongoing colitis
Prior diagnosis of dementia or other primary neurocognitive disorder
Known hypersensitivity/allergy/intolerance to Vancomycin and any ingredients of VE303: sucrose, histidine, yeast extract, cysteine, metabisulfite, and microcrystalline cellulose
History of Roux-en-Y Gastric bypass
Any gastrointestinal surgery in the last year
Substantial immune compromise/deficiency (e.g., uncontrolled human immunodeficiency virus, active immune suppressive therapy including high doses of corticosteroids or medications to prevent graft rejection, recent myeloablative therapy, sustained neutropenia)
Pregnancy or breast feeding
Model for end-stage liver disease (MELD) > 20
History of spontaneous bacterial peritonitis
Hemodialysis in the last 28 days
Placement of a portosystemic shunt or transjugular intrahepatic portosystemic shunt in the last 3 months (permissible if placed >3 months before enrollment)
Unstable doses of opiates, benzodiazepines or other sedating medication
Chronic methadone or low dose benzodiazepines (for example) is acceptable

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Placebo	oral vancomycin	-
VE303	oral vancomycin	VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.
VE303	VE303	VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia.

Primary Outcome Measures

Name	Time	Method
Number of Participants Who Experienced Serious Adverse Events up to Week 6	Week 6	An adverse event (AE) or suspected adverse reaction is considered "serious" if, in the view of the investigator, it results in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect.
Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to Week 6	baseline (pre-vancomycin), Week 6	This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (1+ for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18, where +6 is the best function and -18 is worst function.

Secondary Outcome Measures

Name	Time	Method
Time to Overt HE	up to 26 weeks	This is the number of days from Day 1 of Vancomycin to the first OHE event or to the end of study, whichever came first.
Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26	26 weeks	Shown as a rate (# of episodes/ number of patients) = # per patient.
Adverse Events up to Week 26	up to week 26	total number of AEs
Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26	baseline (pre-vancomycin), week 26	The PROMIS v 1.1 is a 10 question scale where participants select answers from (0) up to (10). Higher scores indicate better quality of life. Results are presented as change in scores pertaining to physical and mental health.
Change in Microbiome Composition From Pre-vancomycin to Week 26	baseline (pre-vancomycin), week 26	This will be calculated by alpha diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this. The Shannon index is a calculation used to measure the diversity of microbial species within a sample, taking into account both the number of different species present (richness) and how evenly distributed their abundances are (evenness). A higher Shannon index indicates a more diverse microbial community, meaning a wider variety of microbes present in roughly equal proportions. The Shannon index was calculated for each sample as part of metagenomic sequencing analysis performed with the tool MetaPhlAn (version 3.0). The minimum Shannon index value is 0 and it could theoretically go to infinity; however, typical values range more in the 1-4 range. Now, this outcome is measuring the CHANGE in Shannon index, therefore negative values are possible, if the diversity of specimens dropped from the pre-vancomycin to the week 26 samples.
PHES From Pre-vancomycin to Week 26	pre-vancomycin up to week 26	This score is a battery of 5 paper-pencil tests that evaluate cognitive and psychomotor processing speed and visuomotor coordination. Scores on each subtest are assigned values based on age-related norms (+1 for scores better than 1 standard deviation (SD) above the normal mean to -3 for scores more than 3 SDs below the normal mean). Combined scores vary from +6 to -18.