FMT-NASH: Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis

Sponsor

Puerta de Hierro University Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03803540

Collaborator

Hospital Universitario Marqués de Valdecilla (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Non-Alcoholic Fatty Liver Disease Non Alcoholic Steatohepatitis	Other: Fecal Microbiota Transplantation	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis, a Pilot Study.

Anticipated Study Start Date :

May 1, 2022

Anticipated Primary Completion Date :

Jan 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Fecal Microbiota Transplantation Lean healthy donor frozen fecal microbiota will be administered via duodenal infusion in an upper gastrointestinal endoscopy	Other: Fecal Microbiota Transplantation Fecal Microbiota Transplantation via duodenal infusion

Arm

Intervention/Treatment

Experimental: Fecal Microbiota Transplantation

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

Other: Fecal Microbiota Transplantation

Fecal Microbiota Transplantation via duodenal infusion

Outcome Measures

Primary Outcome Measures

Efficacy (Histological resolution of NASH defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage) [72 weeks]
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.

Secondary Outcome Measures

Safety (Appearance of adverse events related with Fecal Microbiota Transplantation) [72 weeks]
Appearance of adverse events related with Fecal Microbiota Transplantation will be recorded during 72 weeks follow-up.
Microbiota composition (Changes in microbiota diversity profile related with Fecal Microbiota Transplantation via 16S rRNA analysis) [72 weeks]
Changes in microbiota diversity profile related with Fecal Microbiota Transplantation procedure. 16S rRNA sequencing techniques will be applied on stool samples.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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
Life expectancy lower than two years
Chronic use of steatogenic drugs
Chronic use of immunosuppressants