Evaluation of the Outcome of Fecal Microbiota Transplantation

A Clinical Randomized Controlled Study on the Prevention and Treatment of Drug-refractory Hepatic Encephalopathy After TIPS With Fecal Microbiota Transplantation

Status

Not yet recruiting

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT07454408

Enrollment

Registered

2026-03-06

Start date

2026-03-07

Completion date

2028-06-30

Last updated

2026-03-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fecal Microbiota Transplantation, Hepatic Encephalopathy, TIPS

Keywords

Hepatic Encephalopathy, Fecal Microbiota Transplantation, TIPS, FMT

Brief summary

This study is a randomized, placebo-controlled, exploratory phase II clinical trial led by Professor Han Gyeong-ho from the Digestive Disease Hospital of Xi'an International Medical Center. The study enrolled 40 patients who had experienced recurrence of hepatic encephalopathy despite treatment with rifaximin and lactulose. These patients were randomly divided 1:1 into the experimental group and the control group. After obtaining informed consent from the patients, fecal microbiota transplantation or placebo control was performed. The fecal microbiota was sourced from the feces of healthy individuals who had a rich composition of the Muribaculaceae, Ruminococcaceae, and Bifidobacteriaceae families and did not contain pathogenic bacteria. The safety and efficacy of the treatment were followed up, and blood and fecal samples were collected for sequencing analysis. The aim was to provide new solutions for patients with hepatic encephalopathy who did not respond to the treatment with rifaximin and lactulose after TIPS surgery; and to explore the impact of microbiota changes and translocation on the recurrence of hepatic encephalopathy after TIPS surgery.

Detailed description

This study is a single-center, randomized, placebo-controlled, exploratory phase II clinical trial. A total of 40 patients aged 18-75 years who had drug-refractory hepatic encephalopathy after transjugular intrahepatic portosystemic shunt surgery and experienced at least 2 West Haven grade ≥2 hepatic encephalopathy episodes within 6 months of treatment with lactulose and rifaximin were planned to be enrolled: These patients were randomly assigned in a 1:1 ratio to the fecal microbiota transplantation group and the placebo group. Both groups received basic standard treatment: 1200mg/day of rifaximin + 25ml/once of lactulose, twice/day; The FMT group was additionally infused with fecal suspension (100mL/once, twice/day, for 3 consecutive days) through the nasal jejunostomy tube combined with oral enteric-coated freeze-dried fecal capsules (7 capsules each time, for 1 week), while the placebo group was given the same volume of placebo solution and placebo capsules, with the same frequency and duration as the FMT group. All subjects were followed up at 15 days, 1 month, 3 months, and 6 months after transplantation. The primary outcomes were the safety (adverse events, severe adverse events, FMT-related adverse events) and efficacy (hepatic encephalopathy recurrence rate, time to first recurrence, West Haven classification) of FMT; The secondary outcomes were changes in intestinal flora colonization and diversity, liver function, blood ammonia levels, and health-related quality of life (CLDQ scale). Fecal and blood samples were collected at each follow-up time point for multi-omics detection and analysis. Statistical analysis of the trial data was performed using Kaplan-Meier method, Log-rank test, and Cox proportional hazards regression model.

Interventions

BIOLOGICALFecal Microbiota Transplantation

Fecal microbiota transplantation is used to reconstruct gut microbiota structure, regulate intestinal microecological homeostasis, improve intestinal barrier function, reduce systemic endotoxin load and inflammatory level, for the prevention and treatment of refractory hepatic encephalopathy after TIPS. The preparation is made from stool of qualified screened donors, processed under sterile conditions.

OTHERFMT Matched Placebo

Placebo preparation is identical to fecal microbiota transplantation preparation in appearance, dosage form, administration route and frequency, with no active biological or therapeutic components, used for the control arm of this randomized controlled trial.

DRUGRifaximin、Lactulose

Rifaximin is a non-absorbable oral rifamycin antibiotic, used as standard medical therapy for hepatic encephalopathy, to reduce intestinal urease-producing bacteria and intestinal ammonia production.Lactulose is a synthetic disaccharide laxative, used as first-line standard medical therapy for hepatic encephalopathy, to acidify the intestinal lumen, reduce ammonia production and promote ammonia excretion.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

DOUBLE (Subject, Investigator)

Masking description

This trial adopts a double-blind design for participants and investigators. FMT preparations (nasojejunal infusion solution + enteric-coated capsules) and matched placebo are identical in appearance, dosage form, administration route, frequency and course. Preparations are coded by independent researchers not involved in trial implementation. All participants, investigators, outcome assessors and statisticians will remain blinded to group allocation. The randomization code will be unblinded only after all clinical data are locked, with an emergency unblinding mechanism for serious adverse events.

Intervention model description

This is a single-center, randomized, placebo-controlled, exploratory phase II clinical trial. A total of 40 eligible patients aged 18-75 years with drug-refractory hepatic encephalopathy (HE) after TIPS (≥2 episodes of West Haven ≥2 grade HE within 6 months despite lactulose and rifaximin treatment) will be enrolled. Subjects will be 1:1 randomly assigned to the FMT group or placebo group. Both groups will receive standard HE therapy (rifaximin + lactulose). The FMT group will receive FMT via nasojejunal infusion plus oral capsules, while the control group will receive matched placebo with the same administration regimen. All subjects will be followed up for 6 months to evaluate the safety and efficacy of FMT.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

Yes

Inclusion criteria

* Aged between 18 and 75 years old * Patients who have experienced esophageal-gastric variceal bleeding or recurrent refractory ascites and meet the inclusion criteria, and for whom conservative treatment has failed, are planned to undergo elective TIPS surgery * Patients with recurrent hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS), despite treatment with lactulose and rifaximin (at least 2 episodes of West Haven grade ≥2 HE within 6 months under lactulose and rifaximin intervention) * Provided written informed consent from the patient

Exclusion criteria

* Malignant tumors of the liver, gastrointestinal tract or other systems * Uncontrolled severe active infection (\>grade 2) or sepsis * Spontaneous bacterial peritonitis * Complicated with severe cardiac, renal or pulmonary insufficiency * Other neuropsychiatric diseases, including dementia * Budd-Chiari syndrome * Alcohol dependence or use of psychotropic drugs (benzodiazepines, opioids, etc.) * History of gastrointestinal surgery (e.g., colectomy) within 3 months before enrollment * Pregnant or lactating subjects * Poor compliance judged by the investigator * Model for End-Stage Liver Disease (MELD) score \>17 * Tumor, immunodeficiency, or receiving immunosuppressive therapy within 3 months before enrollment * Patients who have used other prebiotics, probiotics or fecal microbiota transplantation (FMT) before enrollment

Design outcomes

Primary

Measure	Time frame	Description
Incidence and severity of treatment-related adverse events (AEs) and serious adverse events (SAEs)	From the date of randomization to the end of 6-month follow-up after intervention	Record the number, incidence, severity (graded by NCI-CTC v3.0 criteria), correlation with trial intervention, and outcome of all AEs, FMT-related AEs and SAEs in subjects from randomization to the end of follow-up. Key monitoring includes gastrointestinal reactions, infection, exacerbation of hepatic encephalopathy and other intervention-related adverse events.

Secondary

Measure	Time frame	Description
The recurrence rate of hepatic encephalopathy fecal microbiota transplantation intervention	From the date of randomization to the end of 6-month follow-up after intervention	The ratio of the number of patients with recurrent hepatic encephalopathy to the total number of patients in each group
The changes in health-related quality of life after fecal microbiota transplantation intervention	Baseline, 1 month after intervention, 3 months after intervention, 6 months after intervention	The health-related quality of life was evaluated through the Chronic Liver Disease Questionnaire (CLDQ), with the lowest score being 1 and the highest score being 7. The higher the score, the better the health-related quality of life.
The colonization status of the intestinal microbiota	Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention	The survival rate (%) of the donor microbiota in the patient's intestinal tract
Changes in the α diversity of the intestinal microbiota	Baseline, 15 days after intervention, 1 month after intervention, 3 months after intervention, 6 months after intervention	Using metagenomic sequencing technology, the α diversity of the intestinal microbiota (Shannon index, Simpson index) was evaluated.

Countries

China