Clinical trial NCT03467282: Probiotics in NASH Patients - PROBILIVER TRIAL
Official title: Effect of Probiotic Supplementation in Nonalcoholic Steatohepatitis Patients: Randomized Clinical Trial - PROBILIVER TRIAL
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Non-Alcoholic Fatty Liver Disease
Lead sponsor: Hospital de Clinicas de Porto Alegre
Sponsor class: OTHER
First posted: 2018-03-15
Enrollment: 46
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: hepatic fibrosis
timeFrame: 24 weeks
measure: cardiovascular risk
timeFrame: 24 weeks
Secondary outcomes:
measure: diversity of gut microbiota
timeFrame: 24 weeks
measure: inflammation by TLR4 expression
timeFrame: 24 weeks
measure: inflammation by CK18 expression
timeFrame: 24 weeks
measure: inflammation by serum C-reactive protein
timeFrame: 24 weeks
measure: metabolic syndrome
timeFrame: 24 weeks
measure: change in body composition by DEXA
timeFrame: 24 weeks
measure: body composition by bioimpedance
timeFrame: 24 weeks
measure: change in hand grip strength
timeFrame: 24 weeks
measure: change in physical ability
timeFrame: 24 weeks
measure: change in the parameters of sarcopenia by serum myostatin
timeFrame: 24 weeks
measure: change in the parameters of sarcopenia by serum testosterone
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
state: RS
Study officials:
affiliation: Hospital de Clinicas de Porto Alegre
name: Valesca Dall Alba
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.