Probiotics in NASH Patients - PROBILIVER TRIAL
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Interventions
- Dietary Supplement: ProbioticDietary Supplement: Placebo
- Registration Number
- NCT03467282
- Lead Sponsor
- Hospital de Clinicas de Porto Alegre
- Brief 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.
- 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.
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 46
- adult outpatient with diagnostic of NAFLD
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Probiotic Probiotic 1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU Placebo Placebo 1g polydextrose/maltodextrin - twice day
- Primary Outcome Measures
Name Time Method hepatic fibrosis 24 weeks change in the degree of fibrosis by hepatic elastography and scores
cardiovascular risk 24 weeks change in scores and sistemic markers
- Secondary Outcome Measures
Name Time Method diversity of gut microbiota 24 weeks by metagenomics from faecal samples
inflammation by TLR4 expression 24 weeks by ELISA
inflammation by CK18 expression 24 weeks by ELISA
inflammation by serum C-reactive protein 24 weeks by nephelometry
metabolic syndrome 24 weeks reduce in number of metabolic syndrome components
change in body composition by DEXA 24 weeks densitometer GE Medical Systems Lunar Prodigy
body composition by bioimpedance 24 weeks by change in phase angle
change in hand grip strength 24 weeks by manual dynamometry
change in physical ability 24 weeks by walk speed test
change in the parameters of sarcopenia by serum myostatin 24 weeks by ELISA
change in the parameters of sarcopenia by serum testosterone 24 weeks by electrochemiluminescence
Trial Locations
- Locations (1)
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil