Phase 2
N=60
FMT in Cirrhosis and Hepatic Encephalopathy
Cirrhosis · Hepatic Encephalopathy
Bottom Line
View on ClinicalTrials.gov: NCT03796598 ↗Enrolled (actual)
60
Serious AEs
36.7%
Results posted
May 2025
Primary outcome: Primary: Serious Adverse Events Related to FMT — 0; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Fecal Microbial transplant Capsules (Drug); Fecal Microbial Transplant Enema (Drug); Placebo (Other)
- Age
- Adult, Older Adult · 21+ yrs
- Sex
- All
- Sponsor
- VA Office of Research and Development
- Primary completion
- Dec 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Serious Adverse Events Related to FMT |
0; 0; 0; 0 | — |
| SECONDARY Adverse Events Related to FMT |
0; 0; 0; 0 | — |
| SECONDARY Change in Microbial Diversity in Stool |
1.45; 1.46; 1.71; 1.53 | — |
| SECONDARY Sickness Impact Profile Change |
9.63; 15.62; 18.15; 15.94 | — |
| SECONDARY Psychometric Hepatic Encephalopathy Score Performance Change |
-7; -3; -5; -5.5 | — |
| SECONDARY EncephalApp Stroop Off and On Time Change |
218.5; 194.1; 184.8; 235.3 | — |
| SECONDARY Change in Microbial Diversity in Saliva |
1.55; 1.57; 1.57; 1.56 | — |
| SECONDARY HE Related Events |
6; 0; 2; 2 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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 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
Exclusion Criteria
- 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].
- Subjects who are otherwise immunocompetent and have discontinued any immunosuppressant medications 3 or more months prior to enrollment may be eligible to enroll
- Patients on renal replacement therapy
- Patients with untreated, in-situ colorectal cancer
- Patients with a history of chronic intrinsic GI diseases such as inflammatory bowel disease
- ulcerative colitis, Crohn's disease or microscopic colitis
- eosinophilic gastroenteritis or celiac disease
- Major gastro-intestinal or intra-abdominal surgery in the last three months
Other Exclusion Criteria:
- Enema-related
- Platelet count<25,000
- Grade IV hemorrhoids
- Safety-related:
- Dysphagia
- History of aspiration, gastroparesis, intestinal obstruction
- Ongoing antibiotic use (except for Rifaximin)
- Severe anaphylactic food allergy
- Allergy to ingredients Generally Recognized As Safe in the FMT capsules (glycerol, sodium chloride, hypromellose, gellan gum, titanium dioxide, theobroma oil)
- Adverse event attributable to prior FMT
- ASA Class IV or V
- Pregnant or nursing patients
- Acute illness or fever within 48 hours of the day of planned FMT
- Immunocompromised due to medical conditions
- Probiotics use within the last 48 hours of the day of planned FMT
- Any condition that the physician investigators deem unsafe, including other conditions or medications that the investigator determines puts the participant at greater risk from FMT
Data sourced from ClinicalTrials.gov (NCT03796598). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.