Non-Alcoholic Fatty Liver DiseaseNCT04074889
The Effect of Probiotics on the Clinical Outcomes and Gut Microenvironment in Patients With Fatty Liver
A study testing (Microbial cell preparation) Probiotics in people with Non-Alcoholic Fatty Liver Disease, run by Universiti Kebangsaan Malaysia Medical Centre at 1 site in Malaysia.
Trial summary
Fatty liver has been associated with high risk of progression to inflammation of the liver, liver cirrhosis (hardening of the liver), and eventually can lead to liver cancer. So far, the treatment for this condition involves controlling the cholesterol level in the body by practicing low fat diet and daily exercise. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease
- What is being tested?
- (Microbial cell preparation) Probiotics
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteMalaysia
- Study dates
- 30 Aug 2019to Dec 2020
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 and above 2. Diagnosis of NAFLD is confirmed by the presence of fatty liver detected by abdominal ultrasound and controlled attenuation parameter (CAP) score from FibroScan® of >263 3. Raised ALT level (above upper limit of normal): > 35IU/L for males and > 25 IU/L for females
Who cannot join
- Evidence of other chronic liver diseases (as determined by clinical and standard investigations) - e.g. Hepatitis B, C infections, autoimmune hepatic disorders.
- Evidence of acute disorders that affecting the liver - e.g. drug induced liver injury, non-Hepatitis B, C viral infection.
- Biliary disease.
- Liver cancer - primary hepatocellular carcinoma or liver metastasis.
- Evidence of liver cirrhosis.
- Alcohol intake > 20g/day for males and >10g/day for females.
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- Use of steatogenic medications within the past one months - e.g. systemic steroids, methotrexate.
- History of bariatric surgery
- Intake of antibiotics and/or probiotic and proton pump inhibitor within one month before the start of the study or during the study period.
Trial locations and contacts
1 site in 1 country.
Malaysia1 site, 1 recruiting
- Recruiting
The University of Malaysia Medical Centre
Cheras, Kuala Lumpur, 56000
Khairul Najmi Muhammad Nawawi, MBBCh BAO, 0060183734807, khairulnajmi84@gmail.com
Mohamad Hizami Mohamad Nor, MBBCh BAO
About this study
Official title: Study of the Effect of Probiotics on the Clinical Outcomes and Gut Microenvironment in Patients With Non-alcoholic Fatty Liver Disease: a Randomised Controlled Trial
Fatty liver has been associated with high risk of progression to inflammation of the liver, liver cirrhosis (hardening of the liver), and eventually can lead to liver cancer. So far, the treatment for this condition involves controlling the cholesterol level in the body by practicing low fat diet and daily exercise. However, recently there has been evidence that alteration of the normal population of various types of bacteria that lives in the intestines may contributes to the development of fatty liver.
Probiotics is a dietary supplement containing live bacteria that is formulated to change the composition and population of the bacteria in the intestines. It is postulated that by taking specifically formulated probiotics, the alteration of the intestinal bacteria may lead to improvement of the fatty liver, leading to better daily liver function.
In this 6-month study, investigators would like to investigate the effectiveness of the probiotics in improving the liver function and in the treatment of the fatty liver. It will compare the fatty liver of patients who took the probiotics supplements compared to those who did not took it and see if there is any improvement.
Read the detailed description
Non-alcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease nowadays. NAFLD is considered as the hepatic manifestation of metabolic syndrome. In Malaysia, the prevalence of metabolic disorders such as diabetes mellitus, obesity and dyslipidemia are increasing with time. Despite the disease burden, treatments for NAFLD are currently limited due to the ongoing evolving theory of its pathogenesis.
One of the proposed mechanisms is via gut-liver axis (GLA), whereby the role of gut microbiota has been implicated. Two main components of GLA are gut microbiota and gut barrier. A change in gut microbiota composition will predispose to gut barrier dysfunction, which subsequently leads to bacterial by-products translocation into the portal circulation. Eventually, these by-products reach the liver and trigger the cascades of hepatic inflammation, leading to fatty liver and its disease progression.
The aim of this study is to investigate the role of probiotics in modulating the gut microenvironment - namely gut microbiota composition, gut barrier function and local gut inflammation, as well as its effect on the clinical outcomes in NAFLD patients.
Investigators propose a randomised, double-blind, placebo-controlled trial of 6-month duration. Investigators aim to recruit 48 NALFD patients, with either treated with probiotics or placebo. Small intestinal microbiota will be determined by 16S-rRNA sequencing and immunoreactivity of zona occludens-1 (tight junction protein in the gut barrier) and cytokines mRNA level will be measured. The degree of liver steatosis and stiffness will be assessed by using transient elastography and biochemical blood tests. All these variables will be determined pre- and post-intervention with probiotics/placebo.
This study will provide a valuable knowledge on the role of probiotics as the gut microenvironment modulator and strengthen the hypothesis of GLA involvement in the NAFLD development. Hence, probiotics can be strongly considered as one of the treatment options for non-alcoholic fatty liver disease.
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Being tested
- (Microbial cell preparation) Probiotics, Placebo
- Keywords
- Probiotics, Gut Liver Axis
- 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.
(Microbial cell preparation) ProbioticsDietary supplement
Also called Hexbio
Lactobacillus acidophilus (107mg), Lactobacillus casei subsp (107mg), Lactobacillus lactis (107mg), Bifidobacterium bifidum (107mg), Bifidobacterium infantis (107mg) and Bifidobacterium longum (107mg)
PlaceboOther
Placebo sachet with no microbial cell preparation
| Study group | Role | What they receive |
|---|---|---|
| Group A | Active comparator | Patients will be given Lactobacillus \& Bifidobacterium containing probiotics [Lactobacillus acidophilus (107mg), Lactobacillus casei subsp (107mg), Lactobacillus lactis (107mg), Bifidobacterium bifidum (107mg), Bifidobacterium infantis (107mg) and Bifidobacterium longum (107mg], to be taken 1 sachet twice daily for 6 months. Receives: Dietary Supplement: (Microbial cell preparation) Probiotics |
| Group B | Placebo comparator | Patients will be given placebo sachet (exactly the same packaging as active comparator) to be taken 1 sachet twice daily for 6 months. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean difference in hepatic steatosis score
as measured by Controlled Attenuated Parameter score from Transient Elastography (Fibroscan)
Measured: 6-7 months post supplementation
Secondary outcomes (5)
Mean difference in hepatic fibrosis score
as measured by liver stiffness score from Transient Elastography (Fibroscan)
Measured: 6-7 months post supplementation
Mean difference in hepatic steatosis, inflammation and fibrosis scores
as measured by 10 serum biomarkers (LiverFASt)
Measured: 6-7 months post supplementation
Microbiota composition of small intestine
assessed by 16rRNA Amplicon Sequencing
Measured: 6-7 months post supplementation
Mean difference of immunoreactivity score of zona occludens-1 (ZO-1: indicator of intestinal permeability) and CD4+,CD8+, IL-8 (indicator of intestinal mucosal immune system).
Immunohistochemistry
Measured: 6-7 months post supplementation
Mean difference in mRNA expression of genes related to inflammation (IL-6, TNF-alpha, IFN-gamma)
Measured by serum qPCR
Measured: 6-7 months post supplementation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Aug 2019
- Study start30 Aug 2019
- Primary completionJul 2020 (estimated)
- Study completionDec 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Model description
- Randomised, double-blind, placebo-controlled trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universiti Kebangsaan Malaysia Medical Centre
- Sponsor type
- University, hospital or other
- Collaborators
- B-Crobes Laboratory, Fibronostics Pte. Ltd, Ministry of Education, Malaysia
- Responsible party
- Principal investigator, Khairul Najmi, Universiti Kebangsaan Malaysia Medical Centre
- Investigators
- Khairul Najmi Muhammad Nawawi, MBBCh BAO, Principal investigator, The University of Malaysia Medical Centre, Kuala Lumpur, Malaysia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04074889
- Sponsor's protocol ID
- FRGS/1/2018/SKK02/UKM/03/2
- Status last verified
- Aug 2019
- First submitted
- 29 Aug 2019
- Last updated
- 4 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of the Effect of Probiotics on the Clinical Outcomes and Gut Microenvironment in Patients With Non-alcoholic Fatty Liver Disease: a Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT04074889
- Acronym / sponsor ID
- FRGS/1/2018/SKK02/UKM/03/2
- Conditions
- Non-Alcoholic Fatty Liver Disease
- Keywords
- Probiotics, Gut Liver Axis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Universiti Kebangsaan Malaysia Medical CentreUniversity, hospital or other
- Collaborators
- B-Crobes Laboratory, Fibronostics Pte. Ltd, Ministry of Education, Malaysia
- Study start
- 30 Aug 2019 (actual)
- Primary completion
- Jul 2020 (estimated)
- Study completion
- Dec 2020 (estimated)
- First posted
- 30 Aug 2019 (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.
Fatty liver has been associated with high risk of progression to inflammation of the liver, liver cirrhosis (hardening of the liver), and eventually can lead to liver cancer. So far, the treatment for this condition involves controlling the cholesterol level in the body by practicing low fat diet and daily exercise. However, recently there has been evidence that alteration of the normal population of various types of bacteria that lives in the intestines may contributes to the development of fatty liver.
Probiotics is a dietary supplement containing live bacteria that is formulated to change the composition and population of the bacteria in the intestines. It is postulated that by taking specifically formulated probiotics, the alteration of the intestinal bacteria may lead to improvement of the fatty liver, leading to better daily liver function.
In this 6-month study, investigators would like to investigate the effectiveness of the probiotics in improving the liver function and in the treatment of the fatty liver. It will compare the fatty liver of patients who took the probiotics supplements compared to those who did not took it and see if there is any improvement.
Detailed description
Non-alcoholic fatty liver disease (NAFLD) is one of the common causes of chronic liver disease nowadays. NAFLD is considered as the hepatic manifestation of metabolic syndrome. In Malaysia, the prevalence of metabolic disorders such as diabetes mellitus, obesity and dyslipidemia are increasing with time. Despite the disease burden, treatments for NAFLD are currently limited due to the ongoing evolving theory of its pathogenesis.
One of the proposed mechanisms is via gut-liver axis (GLA), whereby the role of gut microbiota has been implicated. Two main components of GLA are gut microbiota and gut barrier. A change in gut microbiota composition will predispose to gut barrier dysfunction, which subsequently leads to bacterial by-products translocation into the portal circulation. Eventually, these by-products reach the liver and trigger the cascades of hepatic inflammation, leading to fatty liver and its disease progression.
The aim of this study is to investigate the role of probiotics in modulating the gut microenvironment - namely gut microbiota composition, gut barrier function and local gut inflammation, as well as its effect on the clinical outcomes in NAFLD patients.
Investigators propose a randomised, double-blind, placebo-controlled trial of 6-month duration. Investigators aim to recruit 48 NALFD patients, with either treated with probiotics or placebo. Small intestinal microbiota will be determined by 16S-rRNA sequencing and immunoreactivity of zona occludens-1 (tight junction protein in the gut barrier) and cytokines mRNA level will be measured. The degree of liver steatosis and stiffness will be assessed by using transient elastography and biochemical blood tests. All these variables will be determined pre- and post-intervention with probiotics/placebo.
This study will provide a valuable knowledge on the role of probiotics as the gut microenvironment modulator and strengthen the hypothesis of GLA involvement in the NAFLD development. Hence, probiotics can be strongly considered as one of the treatment options for non-alcoholic fatty liver disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomised, double-blind, placebo-controlled trial
| Arm | Type | Receives |
|---|---|---|
| Group A | Active comparator | Dietary Supplement: (Microbial cell preparation) ProbioticsPatients will be given Lactobacillus \& Bifidobacterium containing probiotics [Lactobacillus acidophilus (107mg), Lactobacillus casei subsp (107mg), Lactobacillus lactis (107mg), Bifidobacterium bifidum (107mg), Bifidobacterium infantis (107mg) and Bifidobacterium longum (107mg], to be taken 1 sachet twice daily for 6 months. |
| Group B | Placebo comparator | Other: PlaceboPatients will be given placebo sachet (exactly the same packaging as active comparator) to be taken 1 sachet twice daily for 6 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Age 18 and above 2. Diagnosis of NAFLD is confirmed by the presence of fatty liver detected by abdominal ultrasound and controlled attenuation parameter (CAP) score from FibroScan® of >263 3. Raised ALT level (above upper limit of normal): > 35IU/L for males and > 25 IU/L for females
Key exclusion criteria (9 listed)
- Evidence of other chronic liver diseases (as determined by clinical and standard investigations) - e.g. Hepatitis B, C infections, autoimmune hepatic disorders.
- Evidence of acute disorders that affecting the liver - e.g. drug induced liver injury, non-Hepatitis B, C viral infection.
- Biliary disease.
- Liver cancer - primary hepatocellular carcinoma or liver metastasis.
- Evidence of liver cirrhosis.
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 |
|---|---|---|
| (Microbial cell preparation) ProbioticsAlso: HexbioLactobacillus acidophilus (107mg), Lactobacillus casei subsp (107mg), Lactobacillus lactis (107mg), Bifidobacterium bifidum (107mg), Bifidobacterium infantis (107mg) and Bifidobacterium longum (107mg) | Dietary supplement | Group A |
| PlaceboPlacebo sachet with no microbial cell preparation | Other | Group B |
Primary outcome
Mean difference in hepatic steatosis score
Time frame: 6-7 months post supplementation
as measured by Controlled Attenuated Parameter score from Transient Elastography (Fibroscan)
5 secondary outcomes
Mean difference in hepatic fibrosis score
Time frame: 6-7 months post supplementation
Mean difference in hepatic steatosis, inflammation and fibrosis scores
Time frame: 6-7 months post supplementation
Microbiota composition of small intestine
Time frame: 6-7 months post supplementation
Mean difference of immunoreactivity score of zona occludens-1 (ZO-1: indicator of intestinal permeability) and CD4+,CD8+, IL-8 (indicator of intestinal mucosal immune system).
Time frame: 6-7 months post supplementation
Mean difference in mRNA expression of genes related to inflammation (IL-6, TNF-alpha, IFN-gamma)
Time frame: 6-7 months post supplementation
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2019.
- 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.
Khairul Najmi Muhammad Nawawi, MBBCh BAO principal investigator
The University of Malaysia Medical Centre, Kuala Lumpur, Malaysia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing (Microbial cell preparation) Probiotics in people with Non-Alcoholic Fatty Liver Disease, run by Universiti Kebangsaan Malaysia Medical Centre at 1 site in Malaysia.
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 9 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 4 Sep 2019. 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 Malaysia. 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?
Contact Khairul Najmi Muhammad Nawawi, MBBCh BAO (+60183734807, khairulnajmi84@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean difference in hepatic steatosis score (time frame: 6-7 months post supplementation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2019.