CirrhosisPhase 2NCT04899115
VE303 for Treatment of Hepatic Encephalopathy (HE)
A Phase 2 study testing VE303 and oral vancomycin in people with Cirrhosis and Hepatic Encephalopathy, run by Patricia Bloom at 1 site in United States.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cirrhosis, Hepatic Encephalopathy
- What is being tested?
- VE303 and oral vancomycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 6 Aug 2021to 30 Aug 2023
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 20Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy
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.
- Conditions
- Cirrhosis, Hepatic Encephalopathy
- Being tested
- Placebo, VE303, oral vancomycin
- Medical subject headings
- Fibrosis, Hepatic Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
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.
VE303Drug
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 vancomycinDrug
All enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d).
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo; Drug: oral vancomycin |
| VE303 | Experimental | VE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. Receives: Drug: VE303; Drug: oral vancomycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Week 6
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.
Measured: baseline (pre-vancomycin), Week 6
Secondary outcomes (6)
Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26
Shown as a rate (# of episodes/ number of patients) = # per patient.
Measured: 26 weeks
Adverse Events up to Week 26
total number of AEs
Measured: up to week 26
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. Results are presented as change in scores pertaining to physical and mental health.
Measured: baseline (pre-vancomycin), week 26
Time to Overt HE
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.
Measured: up to 26 weeks
Change in Microbiome Composition From Pre-vancomycin to 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.
Measured: baseline (pre-vancomycin), week 26
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.
Measured: pre-vancomycin up to week 26
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start6 Aug 2021
- Primary completion10 Apr 2023
- Study completion30 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Subjects will be randomized 2:1 to VE303 vs placebo. There will be no stratification. After the trial enrolls the first 9 patients, an interim analysis to evaluate safety of VE303 in this population will take place. If there is no concern for a higher rate of Serious adverse events (SAEs) in the VE303 group, enrollment will continue to reach a total of 18 patients.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Patricia Bloom
- Sponsor type
- University, hospital or other
- Collaborators
- Vedanta Biosciences, Inc., American College of Gastroenterology, American Association for the Study of Liver Diseases
- Responsible party
- Sponsor-investigator, Patricia Bloom, University of Michigan
- Investigators
- Patricia Bloom, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04899115
- Sponsor's protocol ID
- HUM00194437
- Status last verified
- Jan 2025
- First submitted
- 19 May 2021
- Last updated
- 7 Feb 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Bloom PP, Bassis CM, Crossette E, Silber JL, Norman JM, Young VB, Lok ASF. Safety and efficacy of a defined bacterial consortium, VE303, to treat HE. Hepatol Commun. 2025 Feb 19;9(3):e0650. doi: 10.1097/HC9.0000000000000650. eCollection 2025 Mar 1.
PubMed 39969428
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial of VE303 to Treat Hepatic Encephalopathy
- ClinicalTrials.gov ID
- NCT04899115
- Acronym / sponsor ID
- HUM00194437
- Conditions
- Cirrhosis, Hepatic Encephalopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Patricia BloomUniversity, hospital or other
- Collaborators
- Vedanta Biosciences, Inc., American College of Gastroenterology, American Association for the Study of Liver Diseases
- Study start
- 6 Aug 2021 (actual)
- Primary completion
- 10 Apr 2023 (actual)
- Study completion
- 30 Aug 2023 (actual)
- First posted
- 24 May 2021 (actual)
- Results
- Posted 7 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Subjects will be randomized 2:1 to VE303 vs placebo. There will be no stratification. After the trial enrolls the first 9 patients, an interim analysis to evaluate safety of VE303 in this population will take place. If there is no concern for a higher rate of Serious adverse events (SAEs) in the VE303 group, enrollment will continue to reach a total of 18 patients.
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Placebo, Drug: oral vancomycin |
| VE303 | Experimental | Drug: VE303, Drug: oral vancomycinVE303 is a live biotherapeutic product comprising 8 nonpathogenic commensal strains of Clostridia. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (20 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PlaceboStarting 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. | Drug | Placebo |
| VE303Starting 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. | Drug | VE303 |
| oral vancomycinAll enrolled subjects will receive 5 days of oral vancomycin 125 mg four times a day (q.i.d). | Drug | Placebo, VE303 |
Primary outcome
Number of Participants Who Experienced Serious Adverse Events up to Week 6
Time frame: 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
Time frame: 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.
6 secondary outcomes
Number of Hospitalizations for Overt Hepatic Encephalopathy (OHE) up to Week 26
Time frame: 26 weeks
Adverse Events up to Week 26
Time frame: up to week 26
Change in Patient Reported Outcome Measurement Information System (PROMIS) Global Health Reported From Pre-vancomycin to Week 26
Time frame: baseline (pre-vancomycin), week 26
Time to Overt HE
Time frame: up to 26 weeks
Change in Microbiome Composition From Pre-vancomycin to Week 26
Time frame: baseline (pre-vancomycin), week 26
PHES From Pre-vancomycin to Week 26
Time frame: pre-vancomycin up to week 26
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39969428Bloom PP, Bassis CM, Crossette E, Silber JL, Norman JM, Young VB, Lok ASF. Safety and efficacy of a defined bacterial consortium, VE303, to treat HE. Hepatol Commun. 2025 Feb 19;9(3):e0650. doi: 10.1097/HC9.0000000000000650. eCollection 2025 Mar 1.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Patricia Bloom, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing VE303 and oral vancomycin in people with Cirrhosis and Hepatic Encephalopathy, run by Patricia Bloom at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 7 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Serious Adverse Events up to Week 6 (time frame: Week 6). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04899115, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025.