Clinical trial NCT03803540: Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis
Official title: Fecal Microbiota Transplantation for the Treatment of Non-Alcoholic Steatohepatitis, a Pilot Study.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Non-Alcoholic Fatty Liver Disease
Non Alcoholic Steatohepatitis
Keywords: Non-Alcoholic Fatty Liver Disease
Non Alcoholic Steatohepatitis
NAFLD
NASH
Fecal Microbiota Transplantation
FMT
Lead sponsor: Puerta de Hierro University Hospital
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Marqués de Valdecilla
First posted: 2019-01-14
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Efficacy (Histological resolution of NASH defined as ballooning disappearance with or without persistence of minimal lobulillar inflammation and no progression of fibrosis stage)
timeFrame: 72 weeks
Secondary outcomes:
measure: Safety (Appearance of adverse events related with Fecal Microbiota Transplantation)
timeFrame: 72 weeks
measure: Microbiota composition (Changes in microbiota diversity profile related with Fecal Microbiota Transplantation via 16S rRNA analysis)
timeFrame: 72 weeks
Other outcomes:
Locations:
city: Majadahonda
country: Spain
facility: Puerta de Hierro University Hospital
state: Madrid
Study officials:
References: