FMT in Cirrhosis and Hepatic Encephalopathy

NCT03796598 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: GAST-001-18SCX001076
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

Patients with end stage of liver disease or cirrhosis can develop confusion due to high ammonia and inflammation. This confusion is brought upon by changes in the bacteria in the bowels and may not respond to current standard of care treatments. Repeated episodes of confusion can make it difficult for patients to function and may result in multiple admissions to the hospital and burden on the family. The investigators have studied using a healthy person's stool to replace the bowel bacteria, called fecal microbial transplant, in small studies with good results. In this trial the investigators propose to perform these procedures using an upper and lower route in Veterans who suffer from this condition and follow them for safety and HE and related hospitalizations over 6 months. The investigators will compare this to placebo treatments and hope that this intervention can improve the health and daily functioning of affected patients.

Conditions

Cirrhosis; Hepatic Encephalopathy

Keywords

fecal microbial transplant; cirrhosis; hepatic encephalopathy

Outcome Measures

Primary Outcomes (1)

• Serious Adverse Events Related to FMT

  Number of patients with serious adverse events between groups related to FMT, especially related to HE

  6 months

Secondary Outcomes (7)

• Adverse Events Related to FMT

  6 months

• Change in Microbial Diversity in Stool

  6 months

• Sickness Impact Profile Change

  30 days and 6 months

• Psychometric Hepatic Encephalopathy Score Performance Change

  60 days

• EncephalApp Stroop Off and On Time Change

  60 days

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Oral and rectal placebo at visit 2 Oral placebo at day 30

Other: Placebo

Group 3: Oral placebo and rectal FMT

ACTIVE COMPARATOR

Oral placebo and rectal FMT at visit 2 Oral placebo at day 30

Drug: Fecal Microbial Transplant Enema; Other: Placebo

Group 2: Oral FMT and rectal placebo

ACTIVE COMPARATOR

Oral FMT and rectal placebo at visit 2 Oral FMT at day 30

Drug: Fecal Microbial transplant Capsules

Group 1: Dual Oral and rectal FMT

EXPERIMENTAL

Dual Oral and rectal FMT at visit 2 Oral FMT at day 30

Drug: Fecal Microbial transplant Capsules; Drug: Fecal Microbial Transplant Enema

Interventions

Fecal Microbial transplant Capsules DRUG

Oral capsules of FMT

Group 1: Dual Oral and rectal FMT; Group 2: Oral FMT and rectal placebo

Fecal Microbial Transplant Enema DRUG

FMT enema

Group 1: Dual Oral and rectal FMT; Group 3: Oral placebo and rectal FMT

Placebo OTHER

Placebo

Group 3: Oral placebo and rectal FMT; Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Cirrhosis diagnosed by either 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 \<100,000 or AST/ALT ratio\>1
• Endoscopic evidence of varices or portal gastropathy
• Fibroscan values suggestive of cirrhosis
• On treatment for hepatic encephalopathy (patient can be on lactulose and rifaximin)
• Able to give written, informed consent (demonstrated by mini-mental status exam\>25 at the time of consenting)
• Women of child bearing potential must agree to use effective contraception for the duration of the study and for 10 days prior and 30 days after the study
• Negative pregnancy test in women of childbearing age

You may not qualify if:

• MELD score \>22
• WBC count \<1000 cells/mm3
• Platelet count\<25,000/mm3
• TIPS in place for less than a month
• Currently on antibiotics apart from rifaximin
• Infection at the time of the FMT (diagnosed by blood culture positivity, urinalysis, paracentesis as needed)
• Hospitalization for any non-elective cause within the last 1 month
• Patients who are pregnant or nursing (will be checked using a urine pregnancy test)
• Patients who are incarcerated
• Patients who are incapable of giving their own informed consent
• Patients who are immuno-compromised due to the following reasons:
• HIV infection (any CD4 count)
• Inherited/primary immune disorders
• Current or recent (\<3 mos) treatment with anti-neoplastic agent
• Current or recent (\<3 mos) treatment with any immunosuppressant medications \[including but not limited to monoclonal antibodies to B and T cells, anti-TNF agents, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine), calcineurin inhibitors (tacrolimus, cyclosporine), mycophenolate mofetil\].

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

Hunter Holmes McGuire VA Medical Center, Richmond, VA

Richmond, Virginia, 23249-0001, United States

Location

Related Publications (2)

• Bajaj JS, Fagan A, Sterling RK, Sikaroodi M, Gallagher ML, Lee H, Matherly SC, Bartels A, Mousel T, Davis BC, Puri P, Fuchs M, Thacker LR, McGinley JP, Khoruts A, Gillevet PM. The multi-omic basis for hepatic encephalopathy recurrence: Analysis of the THEMATIC trial. JHEP Rep. 2025 Oct 18;8(1):101634. doi: 10.1016/j.jhepr.2025.101634. eCollection 2026 Jan.

  PMID: 41503571 DERIVED

• Bloom PP, Bajaj JS. The Current and Future State of Microbiome Therapeutics in Liver Disease. Am J Gastroenterol. 2024 Jan 1;119(1S):S36-S41. doi: 10.14309/ajg.0000000000002581. No abstract available.

  PMID: 38153225 DERIVED

MeSH Terms

Conditions

Fibrosis; Hepatic Encephalopathy

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Results Point of Contact

• Title: Jasmohan Bajaj
• Organization: Richmond VA Medical center

jasmohan.bajaj@va.gov

8046755802

Study Officials

• Jasmohan S. Bajaj, MD MS

  Hunter Holmes McGuire VA Medical Center, Richmond, VA

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: Subjects will be divided into 4 groups via randomization Group 1: Dual oral and rectal FMT, Group 2: Oral FMT and rectal placebo, Group 3: Oral placebo and rectal FMT and Group 4: Oral and rectal placebo

Study Record Dates

• First Submitted: January 3, 2019
• First Posted: January 8, 2019
• Study Start: July 29, 2019
• Primary Completion: December 19, 2023
• Study Completion: December 20, 2023
• Last Updated: May 25, 2025
• Results First Posted: May 25, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)