RecruitingPhase 1NCT06368895

Fecal Microbiota Transplantation by Oral Capsules for Hepatic Encephalopathy Treatment

Efficacy and Safety of Fecal Microbiota Transplantation by Oral Capsules in Patients With Liver


Sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Enrollment

60 participants

Start Date

Apr 7, 2021

Study Type

INTERVENTIONAL

Conditions

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.


Eligibility

Min Age: 18 YearsMax Age: 80 Years

Inclusion Criteria2

  • 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 Criteria11

  • 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

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Interventions

PROCEDUREFecal microbiota transplantation delivery through colonoscopy

Patients will receive 4 L of macrogol and salts solution the afternoon before FMT and remain fasting the night before the scheduled treatment. During colonoscopy, about 350 mL of donor fecal preparation will be infused in the cecum.

DRUGFecal microbiota transplantation delivery through oral capsules

Intestinal gastro-resistant capsules (capacity 0.91 mL, overall 10\^8-9 bacteria per capsule) will be filled with the fecal slurry. From each donation weighing 100 g, it is expected to obtain 150 cps, which will be promptly frozen and stored at -80°C. At each monthly visit, the patient will receive 60 capsules, to be stored at -20°C at home. Capsules will be administered orally at the dose of 1 cps twice a day from month 1 post-colonoscopy to patients in the FMT group 1 (colonoscopy plus capsules), and from day 1 to patients in the FMT group 2 (capsules only).


Locations(1)

Fondazione Policlinico Agostino Gemelli IRCCS

Rome, Italy

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NCT06368895


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