Type2 DiabetesNCT03528707
Effect of Probiotic Co-administration With Omega-3 Fatty Acids on NAFLD
A study testing Symbiter-Omega in people with Type2 Diabetes and NAFLD, run by Bogomolets National Medical University.
Trial summary
One of the potential ideal strategy for NAFLD treatment may be manipulation with gut microbiota. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Omega-3 fatty acids belong to the family of polyunsaturated fatty acids. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Type2 Diabetes, NAFLD, Probiotic
- What is being tested?
- Symbiter-Omega
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- No sites listed yet
- Study dates
- 14 Apr 2015to 28 Jan 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 18 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);
- and presence of active infection, pregnancy or lactation.
About this study
Official title: Effect of Probiotic Co-administration With Omega-3 Fatty Acids on NAFLD: Randomized Clinical Studies
One of the potential ideal strategy for NAFLD treatment may be manipulation with gut microbiota. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Omega-3 fatty acids belong to the family of polyunsaturated fatty acids. They are known to exert a strong positive influence on metabolism and inflammation. The data from animal studies suggested that both probiotics and omega-3 can affect body weight, influence on glucose and fat metabolism, improve insulin sensitivity and reduce chronic systemic inflammation. In respect to experimental data, the current study aim was to provide double-blind single center RCT, for study the efficacy of co-administration of probiotic with omega-3 vs. placebo in type 2 diabetes patient with NAFLD detected on ultrasonography
Read the detailed description
In this single-center double-blind, placebo controlled, parallel group study, 48 type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center were selected. They were randomly assigned to receive "Symbiter Omega" 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 Omega" was supplied by Scientific and Production Company "O.D. Prolisok". It contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), 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 patient received 1 sachet (10 grams) of probiotic-omega 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 start, after inform consent 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
- Type2 Diabetes, NAFLD, Probiotic, Omega-3 Fatty Acids
- Being tested
- Symbiter-Omega, 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.
Symbiter-OmegaDietary supplement
"Symbiter Omega" which contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), supplemented with biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×101
PlaceboDietary supplement
Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day
| Study group | Role | What they receive |
|---|---|---|
| probiotic-omega | Active comparator | Over 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day. Receives: Dietary Supplement: Symbiter-Omega |
| 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 posted18 May 2018
- Study start14 Apr 2015
- Primary completion22 Dec 2015
- Study completion28 Jan 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type2 DiabetesStudies 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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bogomolets National Medical University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Nazarii Kobyliak, Bogomolets National Medical University
- Investigators
- Galyna Mykhalchyshyn, PhD, Principal investigator, Bogomolets National Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03528707
- Sponsor's protocol ID
- ENDO-2
- Status last verified
- Dec 2019
- First submitted
- 1 May 2018
- Last updated
- 17 Dec 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kobyliak N, Abenavoli L, Falalyeyeva T, Mykhalchyshyn G, Boccuto L, Kononenko L, Kyriienko D, Komisarenko I, Dynnyk O. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Minerva Med. 2018 Dec;109(6):418-428. doi: 10.23736/S0026-4806.18.05845-7. Epub 2018 Sep 13.
PubMed 30221912
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotic Co-administration With Omega-3 Fatty Acids on NAFLD: Randomized Clinical Studies
- ClinicalTrials.gov ID
- NCT03528707
- Acronym / sponsor ID
- ENDO-2
- Conditions
- Type2 Diabetes, NAFLD, Probiotic, Omega-3 Fatty Acids
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Bogomolets National Medical UniversityUniversity, hospital or other
- Study start
- 14 Apr 2015 (actual)
- Primary completion
- 22 Dec 2015 (actual)
- Study completion
- 28 Jan 2016 (actual)
- First posted
- 18 May 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.
One of the potential ideal strategy for NAFLD treatment may be manipulation with gut microbiota. Probiotics are defined as live microorganisms that, when administered in adequate amounts, confer a health benefit on the host. Omega-3 fatty acids belong to the family of polyunsaturated fatty acids. They are known to exert a strong positive influence on metabolism and inflammation. The data from animal studies suggested that both probiotics and omega-3 can affect body weight, influence on glucose and fat metabolism, improve insulin sensitivity and reduce chronic systemic inflammation. In respect to experimental data, the current study aim was to provide double-blind single center RCT, for study the efficacy of co-administration of probiotic with omega-3 vs. placebo in type 2 diabetes patient with NAFLD detected on ultrasonography
Detailed description
In this single-center double-blind, placebo controlled, parallel group study, 48 type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center were selected. They were randomly assigned to receive "Symbiter Omega" 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 Omega" was supplied by Scientific and Production Company "O.D. Prolisok". It contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), 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 patient received 1 sachet (10 grams) of probiotic-omega 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 start, after inform consent 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-omega | Active comparator | Dietary Supplement: Symbiter-OmegaOver 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
- 18 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-Omega"Symbiter Omega" which contains combination of flax and wheat germ oil (250 mg of each, concentration of omega-3 fatty acids 1-5%), supplemented with biomass of 14 alive probiotic strains: Lactobacillus + Lactococcus (6×1010 CFU/g), Bifidobacterium (1×101 | Dietary supplement | probiotic-omega |
| PlaceboOver 8 weeks of interventional period, the patient received 1 sachet (10 grams) of gel per day | 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 17 Dec 2019.
- Results publication: PubMed 30221912Kobyliak N, Abenavoli L, Falalyeyeva T, Mykhalchyshyn G, Boccuto L, Kononenko L, Kyriienko D, Komisarenko I, Dynnyk O. Beneficial effects of probiotic combination with omega-3 fatty acids in NAFLD: a randomized clinical study. Minerva Med. 2018 Dec;109(6):418-428. doi: 10.23736/S0026-4806.18.05845-7. Epub 2018 Sep 13.
- 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.
Galyna Mykhalchyshyn, PhD principal investigator
Bogomolets National Medical University
Questions about this trial
What is this clinical trial studying?
A study testing Symbiter-Omega in people with Type2 Diabetes and NAFLD, run by Bogomolets National Medical University.
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 17 Dec 2019. 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?
On the ClinicalTrials.gov record for NCT03528707, which also lists 1 linked publication.
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 17 Dec 2019.