Non-Alcoholic Fatty Liver DiseaseNASHNCT03467282
Probiotics in NASH Patients - PROBILIVER TRIAL
A study testing Probiotic in people with Non-Alcoholic Fatty Liver Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
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… Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- What is being tested?
- Probiotic
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteBrazil
- Study dates
- 29 Nov 2017to 20 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult outpatient with diagnostic of NAFLD
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Brazil1 site
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035003
About this study
Official title: Effect of Probiotic Supplementation in Nonalcoholic Steatohepatitis Patients: Randomized Clinical Trial - PROBILIVER TRIAL
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.
Read the 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
- Being tested
- Probiotic, Placebo
- Medical subject headings
- Non-alcoholic Fatty Liver Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ProbioticDietary supplement
1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU
PlaceboDietary supplement
1g polydextrose/maltodextrin - twice day
| Study group | Role | What they receive |
|---|---|---|
| Probiotic | Experimental | 1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU Receives: Dietary Supplement: Probiotic |
| Placebo | Placebo comparator | 1g polydextrose/maltodextrin - twice day Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
hepatic fibrosis
change in the degree of fibrosis by hepatic elastography and scores
Measured: 24 weeks
cardiovascular risk
change in scores and sistemic markers
Measured: 24 weeks
Secondary outcomes (11)
diversity of gut microbiota
by metagenomics from faecal samples
Measured: 24 weeks
inflammation by TLR4 expression
by ELISA
Measured: 24 weeks
inflammation by CK18 expression
by ELISA
Measured: 24 weeks
inflammation by serum C-reactive protein
by nephelometry
Measured: 24 weeks
metabolic syndrome
reduce in number of metabolic syndrome components
Measured: 24 weeks
change in body composition by DEXA
densitometer GE Medical Systems Lunar Prodigy
Measured: 24 weeks
body composition by bioimpedance
by change in phase angle
Measured: 24 weeks
change in hand grip strength
by manual dynamometry
Measured: 24 weeks
change in physical ability
by walk speed test
Measured: 24 weeks
change in the parameters of sarcopenia by serum myostatin
by ELISA
Measured: 24 weeks
change in the parameters of sarcopenia by serum testosterone
by electrochemiluminescence
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start29 Nov 2017
- Primary completion31 Jul 2020 (estimated)
- Study completion20 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Non-Alcoholic Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital de Clinicas de Porto Alegre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Valesca Dall Alba, Principal investigator, Hospital de Clinicas de Porto Alegre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03467282
- Sponsor's protocol ID
- 160438
- Acronym
- NASH
- Status last verified
- Jun 2020
- First submitted
- 9 Mar 2018
- Last updated
- 19 Jun 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36216309Silva-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.
PubMed 31601229
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotic Supplementation in Nonalcoholic Steatohepatitis Patients: Randomized Clinical Trial - PROBILIVER TRIAL
- ClinicalTrials.gov ID
- NCT03467282
- Acronym / sponsor ID
- NASH / 160438
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Hospital de Clinicas de Porto AlegreUniversity, hospital or other
- Study start
- 29 Nov 2017 (actual)
- Primary completion
- 31 Jul 2020 (estimated)
- Study completion
- 20 Dec 2021 (estimated)
- First posted
- 15 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Probiotic | Experimental | Dietary Supplement: Probiotic1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU |
| Placebo | Placebo comparator | Dietary Supplement: Placebo1g polydextrose/maltodextrin - twice day |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- adult outpatient with diagnostic of NAFLD
Key exclusion criteria (8 listed)
- HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infected patients
- significant intake of alcohol
- cirrhosis,
- pregnant women,
- transplanted patients,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Probiotic1g probiotic mix (twice day): Lactobacillus acidophilus 1x109 CFU + Bifidobacterium lactis 1x109 CFU + Lactobacillus rhamnosus 1x109 CFU + Lactobacillus paracasei 1x109 CFU | Dietary supplement | Probiotic |
| Placebo1g polydextrose/maltodextrin - twice day | Dietary supplement | Placebo |
Primary outcome
hepatic fibrosis
Time frame: 24 weeks
change in the degree of fibrosis by hepatic elastography and scores
cardiovascular risk
Time frame: 24 weeks
change in scores and sistemic markers
11 secondary outcomes
diversity of gut microbiota
Time frame: 24 weeks
inflammation by TLR4 expression
Time frame: 24 weeks
inflammation by CK18 expression
Time frame: 24 weeks
inflammation by serum C-reactive protein
Time frame: 24 weeks
metabolic syndrome
Time frame: 24 weeks
change in body composition by DEXA
Time frame: 24 weeks
body composition by bioimpedance
Time frame: 24 weeks
change in hand grip strength
Time frame: 24 weeks
change in physical ability
Time frame: 24 weeks
change in the parameters of sarcopenia by serum myostatin
Time frame: 24 weeks
change in the parameters of sarcopenia by serum testosterone
Time frame: 24 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2020.
- Derived from this study: PubMed 36216309Barcelos 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.
- Derived from this study: PubMed 31601229Silva-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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Valesca Dall Alba principal investigator
Hospital de Clinicas de Porto Alegre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Probiotic in people with Non-Alcoholic Fatty Liver Disease, run by Hospital de Clinicas de Porto Alegre at 1 site in Brazil.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Jun 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Brazil. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hepatic fibrosis (time frame: 24 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03467282, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Jun 2020.