Probiotics in NASH Patients - PROBILIVER TRIAL

Non-Alcoholic Fatty Liver Disease Clinical Trial

— NASH  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03467282
• Other study ID #: 160438
• Status: Active, not recruiting
• Phase: N/A
• Start date: November 29, 2017
• Est. completion date: December 20, 2021

Study information

• Verified date: June 2020
• Source: Hospital de Clinicas de Porto Alegre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 46
• Est. completion date: December 20, 2021
• Est. primary completion date: July 31, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-Alcoholic Fatty Liver Disease

Intervention

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
1g polydextrose/maltodextrin - twice day

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS

Sponsors (1)

Lead Sponsor	Collaborator
Hospital de Clinicas de Porto Alegre

Country where clinical trial is conducted

Brazil, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	hepatic fibrosis	change in the degree of fibrosis by hepatic elastography and scores	24 weeks
Primary	cardiovascular risk	change in scores and sistemic markers	24 weeks
Secondary	diversity of gut microbiota	by metagenomics from faecal samples	24 weeks
Secondary	inflammation by TLR4 expression	by ELISA	24 weeks
Secondary	inflammation by CK18 expression	by ELISA	24 weeks
Secondary	inflammation by serum C-reactive protein	by nephelometry	24 weeks
Secondary	metabolic syndrome	reduce in number of metabolic syndrome components	24 weeks
Secondary	change in body composition by DEXA	densitometer GE Medical Systems Lunar Prodigy	24 weeks
Secondary	body composition by bioimpedance	by change in phase angle	24 weeks
Secondary	change in hand grip strength	by manual dynamometry	24 weeks
Secondary	change in physical ability	by walk speed test	24 weeks
Secondary	change in the parameters of sarcopenia by serum myostatin	by ELISA	24 weeks
Secondary	change in the parameters of sarcopenia by serum testosterone	by electrochemiluminescence	24 weeks