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NCT Number: NCT06368895

Fecal Microbiota Transplantation by Oral Capsules for Hepatic Encephalopathy Treatment

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.

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Key information

Conditions

Hepatic Encephalopathy Brain Diseases Brain Diseases, Metabolic Central Nervous System Diseases Digestive System Diseases Dysbiosis Hepatic Insufficiency Liver Diseases Liver Failure Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Fondazione Policlinico Agostino Gemelli IRCCS

Rome, 00168, Italy

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Fecal microbiota transplantation delivery through colonoscopy

Procedure

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.

Fecal microbiota transplantation delivery through oral capsules

Drug

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).

Primary outcomes

  1. 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

  2. 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

  1. Evaluation of changes in the gut microbiota composition following the fecal microbiota transplantation

    Time frame: 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).

  2. Evaluation of changes in the systemic inflammatory following the fecal microbiota transplantation

    Time frame: 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

  3. Evaluation of changes in the intestinal inflammatory following the fecal microbiota transplantation

    Time frame: 12 months

    Changes in the intestinal inflammatory condition will be assessed by the quantification of fecal calprotectin concentration (mg/dl).

  4. Comparison between protein metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation

    Time frame: 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.

  5. Comparison between lipid metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation

    Time frame: 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.

  6. Comparison between carbohydrates metabolites concentration (ppm) in serum, urine and feces before and after microbiota transplantation

    Time frame: 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.

Sponsors and collaborators

Lead sponsor

Fondazione Policlinico Universitario Agostino Gemelli IRCCS

Other

Registry information

Official study title

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

Important dates

Study start
2021
Primary completion
2024
Study completion
2024
First posted
Apr 16, 2024
Registry last updated
Sep 18, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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