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Probiotics in NASH Patients - PROBILIVER TRIAL (NASH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03467282
Recruitment Status : Recruiting
First Posted : March 15, 2018
Last Update Posted : August 12, 2019
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Non-Alcoholic Fatty Liver Disease Dietary Supplement: Probiotic Dietary Supplement: Placebo Not Applicable

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 (, 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 46 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Effect of Probiotic Supplementation in Nonalcoholic Steatohepatitis Patients: Randomized Clinical Trial - PROBILIVER TRIAL
Actual Study Start Date : November 29, 2017
Estimated Primary Completion Date : October 31, 2019
Estimated Study Completion Date : December 20, 2021

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

Primary Outcome Measures :
  1. hepatic fibrosis [ Time Frame: 24 weeks ]
    change in the degree of fibrosis by hepatic elastography

Secondary Outcome Measures :
  1. diversity of gut microbiota [ Time Frame: 24 weeks ]
    by metagenomics from faecal samples

  2. inflammation by TLR4 expression [ Time Frame: 24 weeks ]
    by ELISA

  3. inflammation by CK18 expression [ Time Frame: 24 weeks ]
    by ELISA

  4. inflammation by serum C-reactive protein [ Time Frame: 24 weeks ]
    by nephelometry

  5. metabolic syndrome [ Time Frame: 24 weeks ]
    reduce in number of metabolic syndrome components

  6. change in body composition by DEXA [ Time Frame: 24 weeks ]
    densitometer GE Medical Systems Lunar Prodigy

  7. body composition by bioimpedance [ Time Frame: 24 weeks ]
    by change in phase angle

  8. change in hand grip strength [ Time Frame: 24 weeks ]
    by manual dynamometry

  9. change in physical ability [ Time Frame: 24 weeks ]
    by walk speed test

  10. change in the parameters of sarcopenia by serum myostatin [ Time Frame: 24 weeks ]
    by ELISA

  11. change in the parameters of sarcopenia by serum testosterone [ Time Frame: 24 weeks ]
    by electrochemiluminescence

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03467282

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Contact: Valesca Dall Alba 55 51 33597313

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Hospital de Clinicas de Porto Alegre Recruiting
Porto Alegre, RS, Brazil, 90035003
Contact: Valesca Dall Alba         
Sponsors and Collaborators
Hospital de Clinicas de Porto Alegre
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Principal Investigator: Valesca Dall Alba Hospital de Clinicas de Porto Alegre

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Hospital de Clinicas de Porto Alegre Identifier: NCT03467282     History of Changes
Other Study ID Numbers: 160438
First Posted: March 15, 2018    Key Record Dates
Last Update Posted: August 12, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases