Non-Alcoholic Fatty Liver DiseaseNCT03614039
Effect of Probiotic and Smectite Gel on NAFLD
A study testing "Symbiter Forte" in people with Non-Alcoholic Fatty Liver Disease and Fatty Liver, run by Nazarii Kobyliak.
Trial summary
Smectite is a natural silicate clay belonging to the dioctahedral smectite class and has the ability directly to absorb bacterial toxins, bacteria, viruses and bile salts. Diosmectite also has a protective effect against intestinal inflammation hence suppressing production of cytokines such as IL-8 and TNFα. Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Non-Alcoholic Fatty Liver Disease, Fatty Liver, Liver Diseases
- What is being tested?
- "Symbiter Forte"
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 15 Sep 2015to 20 Apr 2016
- 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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- adult participants (ages 18-75, BMI ≥25 kg/m2) diagnosed with NAFLD according to the recommendations of the American Gastroenterology Association (AGA) and American Association for the Study of Liver Disease (AASLD);
- the diagnosis of fatty liver was based on the results of abdominal ultrasonography. Of 4 known criteria (hepato-renal echo contrast, liver brightness, deep attenuation, and vascular blurring), the participants were required to have hepato-renal contrast and liver brightness to be given a diagnosis of NAFLD.
- type 2 diabetes treated with diet and exercise alone or metformin, SUs and insulin at stable dose at least 4 weeks prior to the commencement of the study;
- AST and ALT ≤3x upper limit of normal.
Who cannot join
- alcohol abuse (>20 g/day (2 standard drinks) in women or > 30 g/d (3 drinks) in men over a two-year period);
- chronic viral hepatitis (associated with HBV, HCV, HDV infection);
- drug-induced liver disease, Wilson's disease, hereditary deficiency of antitrypsin-1 and idiopathic hemochromatosis;
- history of decompensated liver disease including ascites, encephalopathy or variceal bleeding;
- regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment;
- antibiotic use within 3 months prior to enrollment;
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- uncontrolled cardiovascular or respiratory disease, active malignancy, or chronic infections;
- use of agents such as vitamin E, omega-3 fatty acids or medications with evidence for effects on NAFLD (pioglitazone, GLP-1 analogues, dipeptidyl peptidase IV inhibitors, ursodeoxycholic acid);
- presence of active infection, pregnancy or lactation.
About this study
Official title: Effect of Alive Probiotics Supplementation With Absorbent Smectite Gel in NAFLD
Smectite is a natural silicate clay belonging to the dioctahedral smectite class and has the ability directly to absorb bacterial toxins, bacteria, viruses and bile salts. Diosmectite also has a protective effect against intestinal inflammation hence suppressing production of cytokines such as IL-8 and TNFα. Investigators suggested that all these pharmacological properties may be beneficial for the treatment of NAFLD. Based on preclinical data, in rats with MSG induced obesity supplementation of alive probiotics with smectite gel (Symbiter-Forte) due to his absorbent activity lead to significant reduction of chronic systemic inflammatory markers, lower total NAS (NAFLD activity score) score, with more pronounced reduction of lobular inflammation as compared to administration of probiotic alone. In respect to preclinical data, in this double-blind single center randomized clinical trial (RCT) the efficacy of alive probiotics supplementation with smectite gel (Symbiter-Forte) vs. placebo in type-2 diabetes patient with NAFLD detected on ultrasonography will be studied
Read the detailed description
In this single-center double-blind, placebo controlled, parallel group study, 50 T2D patients from the Kyiv City Clinical Endocrinology Center - Ukraine, were selected. They were randomly assigned to receive "Symbiter Forte" or placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. Randomization was done by the study statistician based on a computer-generated list. The groups were homogeneous according to age, sex and diagnostic criteria. The assignment of groups was blind to participants, research staff and outcome assessors moreover, to maintain blind parallel study the statistician was not aware of the allocation of participants to intervention.
The "Symbiter Forte" was supplied by Scientific and Production Company "O.D. Prolisok". It contains combination of smectite gel (250 mg), supplemented with biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) genera. Over 8 weeks of interventional period, the patients received 1 sachet (10 grams) of probiotic-smectite and placebo per day. All sachets were identical with similar organoleptic characteristics (e.g., taste and appearance).
The pre-randomization period was designed to minimize the effects of dietary changes on metabolic markers. For this purpose, 2 weeks before the study started, after the informed consent was signed, patients were instructed in one-on-one sessions with a dietitian to follow a therapeutic lifestyle-change diet as classified by the NCEP. In addition, participants were instructed to continue with stable anti-hyperglycemic treatment and received standardized mild physical training for 1 hour per day.
Patients who underwent the study were instructed to take the trial medication as prescribed. Throughout the study, weekly phone follow-up visits were provided for assessment of compliance, adherence to the protocol, as well as the recording of adverse events. The effectiveness of therapy was compared and evaluated separately in the two groups.
- Conditions
- Non-Alcoholic Fatty Liver Disease, Fatty Liver, Liver Diseases, Digestive System Diseases, Type2 Diabetes
- Being tested
- "Symbiter Forte", Placebo
- Keywords
- diosmectite, nutraceuticals, non-alcoholic fatty liver disease, probiotics, Lactobacillus, Bifidobacterium, Propionibacterium
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver, Liver Diseases, Digestive System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
"Symbiter Forte"Dietary supplement
"Symbiter Forte" which contains combination of smectite gel (250 mg), and biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g)
PlaceboDietary supplement
| Study group | Role | What they receive |
|---|---|---|
| probiotic-smectite | Active comparator | Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day. Receives: Dietary Supplement: "Symbiter Forte" |
| placebo | Placebo comparator | Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day. Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
fatty liver index (FLI)
FLI = [e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745)] × 100
Measured: 8 weeks compared to baseline
liver stiffness (LS)
liver stiffness (LS) was measured by Shear Wave Elastography (SWE) and expressed in kPa
Measured: 8 weeks compared to baseline
Secondary outcomes (9)
ALT
ALT in IU/L
Measured: 8 weeks compared to baseline
AST
AST in IU/L
Measured: 8 weeks compared to baseline
γ-GT
γ-GT in IU/L
Measured: 8 weeks compared to baseline
Total Cholesterol (TC)
TC in mmol/l
Measured: 8 weeks compared to baseline
Tryglicerides (TG)
TG in mmol/l
Measured: 8 weeks compared to baseline
LDL-Cholesterol (LDL-C)
LDL-C in mmol/l
Measured: 8 weeks compared to baseline
VLDL-Cholesterol (VLDL-C)
VLDL-C in mmol/l
Measured: 8 weeks compared to baseline
HDL-Cholesterol (HDL-C)
HDL-C in mmol/l
Measured: 8 weeks compared to baseline
cytokines levels
TNF-α, IL-1β, IL-6, IL-8, INF-γ in pg/ml
Measured: 8 weeks compared to baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2018
- Study start15 Sep 2015
- Primary completion15 Mar 2016
- Study completion20 Apr 2016
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
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nazarii Kobyliak
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Nazarii Kobyliak, Bogomolets National Medical University
- Investigators
- Petro Bodnar, Prof, Principal investigator, Bogomolets National Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03614039
- Sponsor's protocol ID
- ENDO-3
- Status last verified
- Aug 2018
- First submitted
- 29 Jul 2018
- Last updated
- 7 Aug 2018
- Results posted
- 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 7 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Alive Probiotics Supplementation With Absorbent Smectite Gel in NAFLD
- ClinicalTrials.gov ID
- NCT03614039
- Acronym / sponsor ID
- ENDO-3
- Conditions
- Non-Alcoholic Fatty Liver Disease, Fatty Liver, Liver Diseases, Digestive System Diseases, Type2 Diabetes
- Keywords
- diosmectite, nutraceuticals, non-alcoholic fatty liver disease, probiotics, Lactobacillus, Bifidobacterium, Propionibacterium
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Nazarii KobyliakUniversity, hospital or other
- Study start
- 15 Sep 2015 (actual)
- Primary completion
- 15 Mar 2016 (actual)
- Study completion
- 20 Apr 2016 (actual)
- First posted
- 3 Aug 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.
Smectite is a natural silicate clay belonging to the dioctahedral smectite class and has the ability directly to absorb bacterial toxins, bacteria, viruses and bile salts. Diosmectite also has a protective effect against intestinal inflammation hence suppressing production of cytokines such as IL-8 and TNFα. Investigators suggested that all these pharmacological properties may be beneficial for the treatment of NAFLD. Based on preclinical data, in rats with MSG induced obesity supplementation of alive probiotics with smectite gel (Symbiter-Forte) due to his absorbent activity lead to significant reduction of chronic systemic inflammatory markers, lower total NAS (NAFLD activity score) score, with more pronounced reduction of lobular inflammation as compared to administration of probiotic alone. In respect to preclinical data, in this double-blind single center randomized clinical trial (RCT) the efficacy of alive probiotics supplementation with smectite gel (Symbiter-Forte) vs. placebo in type-2 diabetes patient with NAFLD detected on ultrasonography will be studied
Detailed description
In this single-center double-blind, placebo controlled, parallel group study, 50 T2D patients from the Kyiv City Clinical Endocrinology Center - Ukraine, were selected. They were randomly assigned to receive "Symbiter Forte" or placebo for 8 weeks, administered as a sachet formulation in double-blind treatment. Randomization was done by the study statistician based on a computer-generated list. The groups were homogeneous according to age, sex and diagnostic criteria. The assignment of groups was blind to participants, research staff and outcome assessors moreover, to maintain blind parallel study the statistician was not aware of the allocation of participants to intervention.
The "Symbiter Forte" was supplied by Scientific and Production Company "O.D. Prolisok". It contains combination of smectite gel (250 mg), supplemented with biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) genera. Over 8 weeks of interventional period, the patients received 1 sachet (10 grams) of probiotic-smectite and placebo per day. All sachets were identical with similar organoleptic characteristics (e.g., taste and appearance).
The pre-randomization period was designed to minimize the effects of dietary changes on metabolic markers. For this purpose, 2 weeks before the study started, after the informed consent was signed, patients were instructed in one-on-one sessions with a dietitian to follow a therapeutic lifestyle-change diet as classified by the NCEP. In addition, participants were instructed to continue with stable anti-hyperglycemic treatment and received standardized mild physical training for 1 hour per day.
Patients who underwent the study were instructed to take the trial medication as prescribed. Throughout the study, weekly phone follow-up visits were provided for assessment of compliance, adherence to the protocol, as well as the recording of adverse events. The effectiveness of therapy was compared and evaluated separately in the two groups.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| probiotic-smectite | Active comparator | Dietary Supplement: "Symbiter Forte"Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day. |
| placebo | Placebo comparator | Dietary Supplement: PlaceboOver 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day. |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- adult participants (ages 18-75, BMI ≥25 kg/m2) diagnosed with NAFLD according to the recommendations of the American Gastroenterology Association (AGA) and American Association for the Study of Liver Disease (AASLD);
- the diagnosis of fatty liver was based on the results of abdominal ultrasonography. Of 4 known criteria (hepato-renal echo contrast, liver brightness, deep attenuation, and vascular blurring), the participants were required to have hepato-renal contrast and liver brightness to be given a diagnosis of NAFLD.
- type 2 diabetes treated with diet and exercise alone or metformin, SUs and insulin at stable dose at least 4 weeks prior to the commencement of the study;
- AST and ALT ≤3x upper limit of normal.
Key exclusion criteria (9 listed)
- alcohol abuse (>20 g/day (2 standard drinks) in women or > 30 g/d (3 drinks) in men over a two-year period);
- chronic viral hepatitis (associated with HBV, HCV, HDV infection);
- drug-induced liver disease, Wilson's disease, hereditary deficiency of antitrypsin-1 and idiopathic hemochromatosis;
- history of decompensated liver disease including ascites, encephalopathy or variceal bleeding;
- regular use of a probiotic or prebiotic supplement within 3 months prior to enrollment;
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 |
|---|---|---|
| "Symbiter Forte""Symbiter Forte" which contains combination of smectite gel (250 mg), and biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×1010/g), Propionibacterium (3×1010/g), Acetobacter (1×106/g) | Dietary supplement | probiotic-smectite |
| Placebo | Dietary supplement | placebo |
Primary outcome
fatty liver index (FLI)
Time frame: 8 weeks compared to baseline
FLI = [e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745) / (1 + e 0.953*loge (triglycerides) + 0.139*BMI + 0.718*loge (ggt) + 0.053*waist circumference - 15.745)] × 100
liver stiffness (LS)
Time frame: 8 weeks compared to baseline
liver stiffness (LS) was measured by Shear Wave Elastography (SWE) and expressed in kPa
9 secondary outcomes
ALT
Time frame: 8 weeks compared to baseline
AST
Time frame: 8 weeks compared to baseline
γ-GT
Time frame: 8 weeks compared to baseline
Total Cholesterol (TC)
Time frame: 8 weeks compared to baseline
Tryglicerides (TG)
Time frame: 8 weeks compared to baseline
LDL-Cholesterol (LDL-C)
Time frame: 8 weeks compared to baseline
VLDL-Cholesterol (VLDL-C)
Time frame: 8 weeks compared to baseline
HDL-Cholesterol (HDL-C)
Time frame: 8 weeks compared to baseline
cytokines levels
Time frame: 8 weeks compared to baseline
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2018.
- 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.
Petro Bodnar, Prof principal investigator
Bogomolets National Medical University
Questions about this trial
What is this clinical trial studying?
A study testing "Symbiter Forte" in people with Non-Alcoholic Fatty Liver Disease and Fatty Liver, run by Nazarii Kobyliak.
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 4 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: finished, as of the sponsor's last update on 7 Aug 2018. Status can change between updates, so confirm with the study contact before making plans.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
fatty liver index (FLI) (time frame: 8 weeks compared to baseline). 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?
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 7 Aug 2018.