Microbiota trAnSplant ThERaPy In hEpatiC Encephalopathy (MASTERPIECE) (MASTERPIECE)

April 9, 2026 updated by: VA Office of Research and Development

Microbiota Transplant Therapy to Prevent HE Recurrence in a Phase 2B Multi-Center Trial of Veterans With Cirrhosis

The goal of this clinical trial is to find out whether changing the microbes in the bowels of Veterans with cirrhosis and hepatic encephalopathy (a condition that affects the brain as a result of liver problems) using capsules made from microbes from healthy people can prevent future episodes of hepatic encephalopathy.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Wartime injuries as well as metabolic disorders can result in liver injury directly or indirectly through PTSD, metabolic disorders, and/or alcohol misuse. These liver injuries culminate in cirrhosis, which affects 4.9 million patients in the US, >80,000 of whom are Veterans. Moreover, numerous Veterans with cirrhosis remain undiagnosed, suggesting these numbers are an underestimation. A major complication of cirrhosis, which is exacerbated by alcohol misuse and PTSD, is hepatic encephalopathy (HE), which affects >50% of Veterans with cirrhosis. Current HE therapies are lactulose (inexpensive but difficult to tolerate) and rifaximin (expensive and second line). However, despite these therapies, a large group of patients have recurrent HE episodes. These recurrences worsen clinical (readmissions, falls, death), psychosocial (cumulative brain injury, poor quality of life, disability, stress on the family), and financial outcomes to the patients, families, and the VHA. Microbiota transplant therapy (MTT) or fecal microbiota transplant (FMT) has the potential to interrupt this cycle. There are Phase 1 and Phase 2a randomized controlled trials (RCTs) published that defined safe and acceptable MTT routes for Veterans with HE. MTT was acceptable to most Veterans who were approached. However, the impact of MTT in preventing HE recurrence in a multi-center context is unclear, especially in those on lactulose only versus those on rifaximin.

The central hypothesis is: Microbial transplant therapy delivered through capsules will significantly reduce the rate of HE recurrence regardless of lactulose or rifaximin use compared to placebo in a multi-center double-blind, placebo-controlled, randomized clinical trial of Veterans with cirrhosis.

In a 6-month double-blind, multi-center, placebo-controlled, randomized clinical trial in Veterans with cirrhosis and HE on lactulose or rifaximin, these specific aims will be used to test this hypothesis:

Aim 1:Determine the rate of HE recurrence in MTT versus placebo-randomized groups: Patients from each site will be randomized 1:1 into receiving MTT or placebo capsules, which will be administered twice a day for 2 weeks. Patients will be followed monthly for 6 months. Recurrence of HE will be defined using standard criteria and will be the primary outcome. Stratification by lactulose use alone or lactulose and rifaximin will be performed.

Aim 2: Determine the effect of MTT on all-cause hospitalizations, death, and liver transplant compared to placebo. This analysis will study safety outcomes other than HE between the groups.

Aim 3: Determine the impact of MTT on systemic inflammation, microbial community structure and function, and donor engraftment over time compared to placebo. In MTT and placebo groups, stool microbiome will be studied for donor engraftment, microbiome structure (stool metagenomics), and microbiome function (targeted and untargeted metabolomics from stool and blood) to determine impact of MTT on recipients and clinical outcomes. Systemic inflammatory changes and antibiotic resistance microbial genes will be analyzed. Individual donor-recipient matching will be studied to evaluate best combinations.

Aim 4: Determine the impact of MTT on cognitive testing, health-related quality of life, and daily function. Cognitive testing, validated PROs, and Veterans' input on FMT and the trial will be analyzed.

Based on favorable results of our single-center phase 2A trial, 162 patients (half on lactulose alone and half on rifaximin) across the three sites will be included. Compound MTP-101C, which is a standardized form of MTT targeting delivery into the distal intestine, will be used. Three rationally selected donors with high Lachnospiraceae relative abundance to maximize engraftment and study donor-recipient matching will be selected.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
162

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Connecticut
      • West Haven, Connecticut, United States, 06516-2770
        • CERC (VISN1, West Haven, CT)
        • Contact:
    • Texas
      • Dallas, Texas, United States, 75216-7167
        • VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX
        • Contact:
    • Virginia
      • Richmond, Virginia, United States, 23249-0001
        • Richmond VA Medical Center, Richmond, VA
        • Contact:
        • Principal Investigator:
          • Jasmohan S. Bajaj, MD MS

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 21 years of age

    • Cirrhosis diagnosed by any of the following in a patient with chronic liver disease

      • Liver Biopsy
      • Radiologic evidence of varices, cirrhosis or portal hypertension
      • Laboratory evidence of platelet count <110,000 or AST/ALT ratio>1
      • Endoscopic evidence of varices or portal hypertensive gastropathy
    • Prior overt HE (patient can be on lactulose and/or rifaximin 4 weeks stable dosing)
    • Able to give written, informed consent [mini-mental status exam (MMSE)]>25 at the time of consenting)
    • For lactulose only group: Prior HE not on rifaximin

Exclusion Criteria:

  • Disease-related:

    • MELD3.0 score>22
    • WBC count<1000
    • non-elective hospitalization or overt HE episode within 1 month
    • on dialysis
    • known untreated, luminal GI cancer
    • chronic intrinsic GI diseases (ulcerative colitis, Crohn's disease, microscopic colitis, eosinophilic gastroenteritis or celiac disease)

  • Safety-related:

    • Current dysphagia
    • History of aspiration, intestinal obstruction or non-medication induced gastroparesis
    • Ongoing absorbable antibiotic use
    • History of anaphylactic food allergy
    • Allergy to ingredients in the capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
  • Adverse event attributable to prior FMT (7) ASA Class V
  • Pregnant or nursing patients
  • Acute illness or fever on the day of planned FMT
  • History of spontaneous bacterial peritonitis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Placebo
Placebo capsule
Other: Placebo capsule
Placebo capsule
Experimental: MTT
Microbiota transplant therapy (MTT) capsules
Biological: Microbiota transplant therapy (MTT) capsules
MTP-101-C is manufactured using cGMP protocols in the Molecular and Cellular Therapeutics (MCT) facility at the University of Minnesota.
Other Names:
  • MTP-101-C

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Recurrence of Hepatic Encephalopathy (HE)
Time Frame: 6 months
HE episodes that requires hospitalization, ER visits, or medication changes prompted under medical supervision.
6 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Death
Time Frame: 6 months
Death
6 months
Non-elective Hospitalizations
Time Frame: 6 months
Cirrhosis-related, relatedness to MTT or all-cause
6 months
Liver transplant
Time Frame: 6 months
Liver transplant
6 months
Health-related quality of life (HRQOL) assessment: Patient-Reported Outcomes Measurement Information System-29 (PROMIS-29)
Time Frame: 6 months
PROMIS-29 used 29 items that are scored using T-scores (mean = 50, SD = 10) Maximum 100, minimum 0. Changes in t-scores between and within groups will be studied. High score=better
6 months
Health-related quality of life (HRQOL) assessment: Sickness Impact Profile (SIP)
Time Frame: 6 months
SIP is a 136-item self-report questionnaire assessing health-related dysfunction, yielding a total score (0-100%) and 12 category scores. Higher scores indicate greater dysfunction (worse health). Items are yes/no, weighted based on severity, and sum into physical and psychosocial dimensions.
6 months
Cognitive testing: Psychometric Hepatic Encephalopathy score (PHES)
Time Frame: 6 months
Psychometric Hepatic Encephalopathy score is a battery of 5 paper-and-pencil tests (NCT-A, NCT-B, SDT, LTT, DST) used to detect minimal hepatic encephalopathy (MHE), often requiring 15 minutes to complete. It measures cognitive speed, attention, and motor skills, with results adjusted for age and education, typically yielding a sum score -4 indicating impairment. Low score indicates worse performance.
6 months
Cognitive testing: EncephalApp Stroop
Time Frame: 6 months
Stroop testing results: measures response times in two phases-"OFF" (simple) and "ON" (complex/incongruent)-to detect covert hepatic encephalopathy (CHE). A total OffTime+OnTime based on local norms suggests impairment, with higher scores indicating worse performance
6 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Safety laboratories: Model for End-stage Liver Disease 3.0 (MELD3.0 score)
Time Frame: 6 months
MELD3.0 score is a validated blood laboratory score of INR, bilirubin, creatinine, albumin and gender. High score=worse prognosis
6 months
Serum ammonia
Time Frame: 6 months
Serum ammonia levels will be drawn and analyzed using local clinical laboratories.
6 months
Pathophysiological: Microbiota changes
Time Frame: 6 months
Stool microbiota composition and functional change including serum metabolomics
6 months
Pathophysiological: Inflammation
Time Frame: 6 months
Serum inflammatory cytokines
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
VA Office of Research and Development

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Jasmohan S. Bajaj, MD MS, Richmond VA Medical Center, Richmond, VA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 30, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 31, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 3, 2031

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 2, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 9, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GAST-006-25S
  • IRBnet1909366 (Other Identifier: VA Central IRB)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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