Fecal Microbiota Transplantation by Oral Capsules for Hepatic Encephalopathy Treatment

Phase 1

Recruiting

• Conditions: Hepatic Encephalopathy; Dysbiosis
• Interventions: Procedure: Fecal microbiota transplantation delivery through colonoscopy; Drug: Fecal microbiota transplantation delivery through oral capsules

• Registration Number: NCT06368895
• Lead Sponsor: Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Brief Summary

This interventional study aims to evaluate the safety and efficacy of oral capsule fecal microbiota transplantation (FMT) for treating hepatic encephalopathy refractory to conventional rifaximin and lactulose therapy in patients with liver cirrhosis. Patients diagnosed with hepatic encephalopathy refractory to rifaximin and lactulose therapy will be randomized into three groups. While continuing conventional therapy, the first group receives FMT via colonoscopy and oral capsule administration, the second group receives only oral capsule administration, and the third group serves as a control, receiving only conventional therapy.

The aims of the study are:

To evaluate the efficacy and safety of FMT by oral capsules in cirrhotic patients with hepatic encephalopathy refractory to standard therapy.

To evaluate changes in the gut microbiota composition and in the intestinal and systemic inflammatory condition occurring after FMT and if they can be associated with clinical improvement.

To evaluate metabolic modifications occurring after FMT and if they can be associated with clinical improvement.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-07
• Status Verified: 2024-04
• Study First Submitted: 2024-04-04
• Study First Submitted QC: 2024-04-11
• Last Update Submitted: 2024-04-11
• Study First Posted: 2024-04-16
• Last Update Posted: 2024-04-16
• Primary Completion: 2025-06
• Study Completion: 2025-06

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• Diagnosis of liver cirrhosis
• Hepatic encephalopathy of grade >1 or higher according to West Haven classification, persistent or recurrent despite treatment with lactulose/lactitol and rifaximin at adequate doses started at least 30 days before the Hepatic encephalopathy episode

Exclusion Criteria

• Na <130 meq /l
• Creatinine > 1.3 mg / dl
• Presence of grade 3 ascites
• Presence of esophagogastric varices at risk of haemorrhage in the absence of adequate prophylaxis
• Presence of other possible causes of encephalopathy (cerebral vascular disease, known neurodegenerative or cognitive disorders)
• Known psychiatric disorders or other causes of brain dysfunction (e.g. hypoglycemia, hyponatremia)
• Alcohol consumption
• Diagnosis of hepatocellular carcinoma
• Contraindication to fecal microbiota transplantation (e.g. pregnancy or breastfeeding)
• Presence of known intestinal diseases
• Any clinical condition that, in the opinion of the investigators, may contraindicate the enrollment in the study

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Fecal microbiota transplantation through colonoscopy and oral capsules	Fecal microbiota transplantation delivery through colonoscopy	Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo a two-stage fecal microbiota transplantation: initial colonoscopic delivery followed by daily oral capsules administration one month later. Patients will continue also conventional therapy with rifaximin and lactulose
Fecal microbiota transplantation through colonoscopy and oral capsules	Fecal microbiota transplantation delivery through oral capsules	Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo a two-stage fecal microbiota transplantation: initial colonoscopic delivery followed by daily oral capsules administration one month later. Patients will continue also conventional therapy with rifaximin and lactulose
Fecal microbiota transplantation through oral capsules	Fecal microbiota transplantation delivery through oral capsules	Patients with cirrhosis and hepatic encephalopathy refractory to conventional treatment will undergo fecal microbiota transplantation through daily oral capsules administration. Patients will continue also conventional therapy with rifaximin and lactulose.

Primary Outcome Measures

Name	Time	Method
Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy	12 months	Number of patients with treatment associated adverse events as assessed by CTCAE v5.0
Evaluation of efficacy of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy	12 months	Number of patients with an improvement or no worsening of hepatic encephalopathy after treatment administration as clinically assessed by West-Haven classification and psychometric tests (portosystemic hepatic encephalopathy syndrome test and inhibitory control test) and through laboratory measurement of ammonia serum levels.

Secondary Outcome Measures

Name	Time	Method
Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation	12 months	DNA and RNA microbiota sequencing on fecal samples will be performed every three months after treatment initiation to define changes in the abundance of bacteria and alpha diversity (by the Simpson's Index of Diversity).
Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation	12 months	Changes in the systemic inflammatory condition will be assessed by the quantification of serum cytokines, chemokines, and bacterial fragments concentrations (units/ml): Interleukin1 beta, tumor necrosis factor alpha, Interleukin2, Interleukin6, Interleukin17, interferon gamma, Chemokine C-C motif ligand 2, Chemokine C-C motif ligand 3, Chemokine C-C motif ligand 4, Chemokine C-C motif ligand 5, Chemokine C-C motif ligand 10, Chemokine C-X-C motif ligand 10, lipopolysaccharides
Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation	12 months	Changes in the intestinal inflammatory condition will be assessed by the quantification of fecal calprotectin concentration (mg/dl).
Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation	12 months	Quantification of amino acides will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods.
Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation	12 months	Quantification of fatty acids, acyl carnitine, tryglicerides, dyacil glycerols and phospholipides will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods.
Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation	12 months	Quantification of tricarboxylic acid cycle compounds, sugars and sugar phosphates will be performed before the microbiota transplantation and every three months after by the examination of serum, urine and fecal samples through liquid chromatography tandem mass spectrometry methods.

Trial Locations

Locations (1)

Fondazione Policlinico Agostino Gemelli IRCCS; 🇮🇹 Rome, Italy