Probiotics in NASH Patients - PROBILIVER TRIAL

NCT ID: NCT03467282

Last Updated: 2020-06-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 46 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-29
• Study Completion Date: 2021-12-20

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.

Conditions

Non-Alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Probiotic

1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU

Group Type: EXPERIMENTAL

Probiotic

Intervention Type: DIETARY_SUPPLEMENT

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DIETARY_SUPPLEMENT

1g polydextrose/maltodextrin - twice day

Interventions

Probiotic

1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU

Intervention Type: DIETARY_SUPPLEMENT

Placebo

1g polydextrose/maltodextrin - twice day

Intervention Type: DIETARY_SUPPLEMENT

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital de Clinicas de Porto Alegre

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Valesca Dall Alba

Role: PRINCIPAL_INVESTIGATOR

Hospital de Clinicas de Porto Alegre

Locations

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, Brazil

Countries

Brazil

References

Barcelos STA, Silva-Sperb AS, Moraes HA, Longo L, de Moura BC, Michalczuk MT, Uribe-Cruz C, Cerski CTS, da Silveira TR, Dall'Alba V, Alvares-da-Silva MR. Oral 24-week probiotics supplementation did not decrease cardiovascular risk markers in patients with biopsy proven NASH: A double-blind placebo-controlled randomized study. Ann Hepatol. 2023 Jan-Feb;28(1):100769. doi: 10.1016/j.aohep.2022.100769. Epub 2022 Oct 8.

Reference Type: DERIVED

PMID: 36216309 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31601229 (View on PubMed)

Other Identifiers

160438

Identifier Type: -

Identifier Source: org_study_id