VE303 for Treatment of Hepatic Encephalopathy (HE)

Cirrhosis Clinical Trial

Official title:

A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04899115
• Other study ID #: HUM00194437
• Status: Completed
• Phase: Phase 2
• Start date: August 6, 2021
• Est. completion date: August 30, 2023

Study information

• Verified date: April 2024
• Source: University of Michigan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: August 30, 2023
• Est. primary completion date: April 10, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Brain Diseases
• Cirrhosis
• Hepatic Encephalopathy

Intervention

Drug:
• Placebo
Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of placebo for 14 days taken once daily.
• VE303
Starting the last day of oral vancomycin (Day 1), subjects randomized to this arm will take 5 capsules of VE303 taken daily for 14 days. The quantity of each strain is proportioned to assure a specific per-strain per-capsule titer. The 8 strains are blended together with a micro-crystalline cellulose flow agent and placed in enteric capsules.
• oral vancomycin
All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan

Sponsors (4)

Lead Sponsor	Collaborator
Patricia Bloom	American Association for the Study of Liver Diseases, American College of Gastroenterology, Vedanta Biosciences, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants Who Experienced Serious Adverse Events up to 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.	Week 6
Primary	Change in Psychometric Hepatic Encephalopathy Score (PHES) as a Measure of Cognitive Function From Pre-vancomycin to 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.	baseline (pre-vancomycin), Week 6
Secondary	Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26		up to week 26
Secondary	Adverse Events up to Week 26		up to week 26
Secondary	Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to 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.	baseline (pre-vancomycin), week 26
Secondary	Time to Overt HE		up to 26 weeks
Secondary	Change in Microbiome Composition From Pre-vancomycin to Week 26	This will be calculated by beta diversity between stool collection timepoints and will have metagenomic sequencing on stool to assess this.	baseline (pre-vancomycin), week 26
Secondary	Change in Serum and Stool Biomarkers From Pre-vancomycin to Week 26		baseline (pre-vancomycin), week 26
Secondary	PHES From Pre-vancomycin 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.	pre-vancomycin up to week 26