Probiotics in NASH Patients - PROBILIVER TRIAL (NASH)

Effect of Probiotic Supplementation in Nonalcoholic Steatohepatitis Patients: Randomized Clinical Trial - PROBILIVER TRIAL

Non-alcoholic Fatty Liver Disease (NAFLD) is characterized by excessive accumulation of lipids in hepatocytes, not associated with alcohol consumption and ranges from hepatic steatosis to steatohepatitis, a form that can progress to cirrhosis or hepatocarcinoma, and is considered a liver manifestation of the metabolic syndrome (MetS). The disease occurs in 16 - 30% of the general population, but can reach up to 90% of obese individuals. Changes in lifestyle, including weight loss and physical activity are indicated with first choices for improvement of the liver condition.

Recently the relationship between obesity, diabetes, MetS and NAFLD with intestinal microbiota has also been suggested in the development and progression of liver disease, since it is related to hepatic steatosis and inflammation. In this sense, this work aims to evaluate the effects of probiotic supplementation on intestinal microbiota modulation, degree of hepatic fibrosis and steatosis, inflammation and body composition.

Study Overview

• Status: Unknown
• Conditions: Non-Alcoholic Fatty Liver Disease
• Intervention / Treatment: Dietary supplement: Probiotic; Dietary supplement: Placebo

Detailed Description

In this randomized clinical trial (RCT) will include adult outpatients linked to the Gastroenterology Service of the Hospital de Clínicas de Porto Alegre (Hospital of Clinics of Porto Alegre-HCPA) -Brazil with diagnosis of NAFLD confirmed by biopsy and transient elastography. Patients who are cirrhotic, pregnant, co-infected or who have Chronic Kidney Disease will not be included. All patients, after signing the Written Informed Consent Form, will undergo a complete anamnesis to investigate alcohol consumption (AUDIT, Alcohol Use Disorders Identification Test), smoking, previous history, medications in use, food consumption assessment (through a 3-day food record), physical activity level and physical and functional capacity (International Physical Activity Questionnaire, sit-to-stand test, unipodal, walk test and dynamometry), body composition (Electrical bioimpedance, dual energy x-ray absorptiometry (DEXA), anthropometric measurements), cardiovascular risk (Framingham Score and Atherosclerotic Cardiovascular Disease - ASCVD), biochemical parameters for assessment of inflammatory status [C-reactive protein (CRP), toll-like receptor 4 (TLR4)], lipid profile (total cholesterol, HDL, LDL, triglycerides), hepatic function [cytokeratin-18 (CK18), aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-glutamyltransferase (GGT), bilirubin, alkaline phosphatase], as well as blood glucose level , insulin, albumin, creatinine and complete blood count and even assessment of gut microbiota (patients will be provided with a kit for collecting feces and from the extraction of DNA from stool samples, after which a metagenomic analysis will be performed). These procedures will be performed at baseline and repeated after 24 weeks (at the end of the study). Through the of process of randomization (randomization.com), the patients will be allocated to receive treatment A or B. As for patients and researchers involved both are blinded (double-blind study). The intervention consists of treatment with probiotic mix (Lactobacillus acidophilus 1x109 colony-forming unit (CFU) + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU) and the placebo identical in characteristics and packaging (polydextrose/maltodextrin). Patients will be instructed to consume 2 sachets/day during 24 weeks. Patients will be instructed to report any symptoms or para effects related to the use of sachets and adherence control will be carried out through the patient's notes on a form provided and also by checking the number of sachets.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035003
      • Hospital de Clínicas de Porto Alegre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• adult outpatient with diagnostic of NAFLD

Exclusion Criteria:

• HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients
• significant intake of alcohol
• cirrhosis,
• pregnant women,
• transplanted patients,
• intake of supplements or foods containing probiotics,
• immunosuppressants, antibiotics, corticosteroids, valproic acid and amiodarone,
• other chronic inflammatory diseases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Probiotic; 1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU	Dietary supplement: Probiotic; 1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU
Placebo Comparator: Placebo; 1g polydextrose/maltodextrin - twice day	Dietary supplement: Placebo; 1g polydextrose/maltodextrin - twice day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
hepatic fibrosis	change in the degree of fibrosis by hepatic elastography and scores	24 weeks
cardiovascular risk	change in scores and sistemic markers	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diversity of gut microbiota	by metagenomics from faecal samples	24 weeks
inflammation by TLR4 expression	by ELISA	24 weeks
inflammation by CK18 expression	by ELISA	24 weeks
inflammation by serum C-reactive protein	by nephelometry	24 weeks
metabolic syndrome	reduce in number of metabolic syndrome components	24 weeks
change in body composition by DEXA	densitometer GE Medical Systems Lunar Prodigy	24 weeks
body composition by bioimpedance	by change in phase angle	24 weeks
change in hand grip strength	by manual dynamometry	24 weeks
change in physical ability	by walk speed test	24 weeks
change in the parameters of sarcopenia by serum myostatin	by ELISA	24 weeks
change in the parameters of sarcopenia by serum testosterone	by electrochemiluminescence	24 weeks

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Valesca Dall Alba, Hospital de Clínicas de Porto Alegre

Publications and helpful links

General Publications

• Silva-Sperb AS, Moraes HA, de Moura BC, Alves BC, Bruch-Bertani JP, Azevedo VZ, Dall'Alba V. Effect of probiotic supplementation in nonalcoholic steatohepatitis patients: PROBILIVER TRIAL protocol. Trials. 2019 Oct 10;20(1):580. doi: 10.1186/s13063-019-3679-7.

Study record dates

Study Major Dates

• Study Start (Actual): November 29, 2017
• Primary Completion (Anticipated): July 31, 2020
• Study Completion (Anticipated): December 20, 2021

Study Registration Dates

• First Submitted: March 9, 2018
• First Submitted That Met QC Criteria: March 9, 2018
• First Posted (Actual): March 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 19, 2020
• Last Update Submitted That Met QC Criteria: June 17, 2020
• Last Verified: June 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 160438

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No