Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis

NCT03803540 | Unknown Phase 1

• 1 other identifier: FMT-NASH
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Human microbiota is the set of microorganisms that, in a symbiotic way, coexist and develop in the different surfaces (skin and mucous membranes) of the human body. It is estimated that it is composed of approximately 10\^14 bacteria and other unicellular life forms . The gastrointestinal (GI) tract is the organ in which the microbiota reaches its greatest complexity, influencing its metabolic activities in different organs and human systems. Human microbiota plays a role in multiple homeostatic and physiological functions including energy and intermediary metabolism, normal immune responses, and even appropriate bowel development and nervous system functioning. Given its vascular supply, the liver plays important roles in metabolism and immunological functions. It receives 70% of blood supply through the portal vein which carries all metabolic products derived from GI microbiota. Non alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in developed countries (with an estimated prevalence around 25 - 40% of adults) and it is expected that the burden of disease will increase in the near future. This condition can progress through a spectrum of progressive liver damage to non alcoholic steatohepatitis (NASH), liver fibrosis, cirrhosis and liver cancer. Around 20-30% of NAFLD patients develop NASH, with a lower rate progressing further to fibrosis and cirrhosis. Currently, there is no approved pharmacological or interventional treatment for the management of this so prevalent disease, apart from changes in lifestyle aiming weight loss. The aim of the present pilot study is to assess the efficacy and safety of microbiota manipulation by means of Fecal Microbiota Transplantation in the treatment of patients with NASH.

Conditions

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis

Keywords

Non-Alcoholic Fatty Liver Disease; Non Alcoholic Steatohepatitis; NAFLD; NASH; Fecal Microbiota Transplantation; FMT

Outcome Measures

Primary Outcomes (1)

• Efficacy (Histological resolution of NASH defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage)

  Two liver biopsy samples (one pre-FMT and the second 72 weeks after FMT) will be taken. Resolution of NASH is defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage. NAFLD Activity Score is the histological scale that will be used.

  72 weeks

Secondary Outcomes (2)

• Safety (Appearance of adverse events related with Fecal Microbiota Transplantation)

  72 weeks

• Microbiota composition (Changes in microbiota diversity profile related with Fecal Microbiota Transplantation via 16S rRNA analysis)

  72 weeks

Study Arms (1)

Fecal Microbiota Transplantation

EXPERIMENTAL

Lean healthy donor frozen fecal microbiota will be administered via duodenal infusion in an upper gastrointestinal endoscopy

Other: Fecal Microbiota Transplantation

Interventions

Fecal Microbiota Transplantation OTHER

Fecal Microbiota Transplantation via duodenal infusion

Fecal Microbiota Transplantation

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Body Mass Index \> 30 Kg / m\^2
• Histological evidence of NASH (by means of hepatic percutaneous biopsy obtained in the previous six months) defined as at least 1 point in each category of NAFLD Activity Score with a fibrosis stage between 0 and 3.
• Global NAFLD Activity Score \>= 4 points
• For patients with fibrosis stage 0 or 1, NAFLD Activity Score should be \>= 5 points and they should have one of the following comorbidities: Metabolic Syndrome, type 2 diabetes mellitus or Homeostasis Model Assessment - Insulin Resistance (HOMA-IR) \> 6.

You may not qualify if:

• Patients unable or unwilling to give the informed consent
• Patients actively participating in another clinical trial or investigational protocol
• Cirrhosis of the liver: Transient elastography \> 20 kilopascal or histological evidence of it (grade 4 fibrosis)
• Alcoholic consumption greater than 14 g / week in women or 21 g / week in men
• Any significant hepatic comorbidity: chronic active viral hepatitis, cholestatic disease, hemochromatosis or Wilson disease
• HIV infection
• Liver transplantation
• Hepatocellular carcinoma
• Women during pregnancy or breastfeeding
• Portal thrombosis
• Non-cirrhotic portal hypertension
• Gastroesophageal varices
• Previous gastrointestinal tract major surgery (excluding appendectomy and cholecystectomy)
• Previous Fecal Microbiota Transplantation
• Chronic significant kidney or heart disease

Sponsors & Collaborators

• Puerta de Hierro University Hospital: lead
• Hospital Universitario Marqués de Valdecilla: collaborator

Study Sites (1)

Puerta de Hierro University Hospital

Majadahonda, Madrid, 28222, Spain

Location

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of the department of Gastroenterology and Hepatology

Study Record Dates

• First Submitted: January 9, 2019
• First Posted: January 14, 2019
• Study Start: May 1, 2022
• Primary Completion: January 1, 2023
• Study Completion: April 1, 2023
• Last Updated: April 14, 2022

Record last verified: 2022-04

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)