Efficacy and Safety of Fecal Microbiota Transplantation by Oral Capsules in Patients With Liver
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 80 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Fecal microbiota transplantation through colonoscopy and 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
Intervention: Fecal microbiota transplantation delivery through colonoscopy (Procedure)
Fecal microbiota transplantation through colonoscopy and 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
Intervention: Fecal microbiota transplantation delivery through oral capsules (Drug)
Fecal microbiota transplantation 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.
Intervention: Fecal microbiota transplantation delivery through oral capsules (Drug)
Outcomes
Primary Outcomes
Evaluation of safety of fecal microbiota transplantation by oral capsules in the treatment of cirrhotic patients with hepatic encephalopathy refractory to conventional therapy
Time Frame: 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
Time Frame: 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 Outcomes
- Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation(12 months)
- Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation(12 months)
- Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation(12 months)
- Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation(12 months)
- Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation(12 months)
- Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation(12 months)