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Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Adults NAFLD Patients (DELI_NAFLD Study)

Primary Purpose

Non-Alcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver, Hepatic Steatosis

Status
Recruiting
Phase
Not Applicable
Locations
Ukraine
Study Type
Interventional
Intervention
Probiotic lysate (postbiotic and metabiotc)
Placebo
Sponsored by
Bogomolets National Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Alcoholic Fatty Liver Disease focused on measuring Postbiotics, metabiotics, L. rhamnosus, L. delbrueckii, Obesity, Non-Alcoholic Fatty Liver Disease

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: adult participants (ages 18-70) presence of NAFLD diagnosed 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 MRI-PDFF of at least 6.4%; fatty liver index (FLI) more than 60; BMI 25-39.9 kg/m2; aspartate transaminase (AST) and alanine transaminase (ALT) ≤3x upper limit of normal; written informed consent. Exclusion Criteria: recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface antigen) or hepatitis C (hepatitis C antibody); alcohol abuse (>20 g/day (2 standard drinks) in women or > 30 g/d (3 drinks) in men over a two-year period); 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 an agents with gut microbiota modulation activity (antibiotic, pro-, pre-, post or synbiotics supplement etc.) within 3 months prior to enrollment; allergy on probiotics or their components; 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); subjects with a history of bariatric surgery or significant weight loss (> 5% body weight) or rapid weight loss (> 1.6kg/week), within 6 months prior to enrollment; uncontrolled cardiovascular or respiratory disease, decompensated liver disease including ascites, encephalopathy or variceal bleeding, active malignancy, or chronic infections; participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks prior to enrollment; participation in other clinical trials; presence of pregnancy or lactation.

Sites / Locations

  • Bogomolets National Medical UniversityRecruiting
  • Kyiv City Clinical Endocrinology CenterRecruiting
  • Center for Innovative Medical Technologies of the National Academy of Sciences of UkraineRecruiting
  • Danylo Halytsky Lviv National Medical UniversityRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Probiotic lysate (postbiotic and metabiotc) group

Placebo group

Arm Description

oral, 2 capsules per day (BID) for 3 month treatment

placebo, oral, 2 capsules per day (BID) for 3 month treatment

Outcomes

Primary Outcome Measures

changes in hepatic fat content
will be measured by magnetic resonance proton density fat fraction (MRI-PDFF) in %
changes in hepatic fat content
will be measured by ultrasound attenuation coefficient measurement (ACM) in dB/cm
changes in 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

Secondary Outcome Measures

hepatic steatosis index (HSI)
HSI = 8 x ALT/AST + BMI(+ 2 if type 2 diabetes yes, + 2 if female)
ALT
in IU/L
AST
AST in IU/L
GGT
GGT in IU/L
liver stiffness (LS)
liver stiffness (LS) will be measured by Shear Wave Elastography (SWE) and expressed in kPa
TyG index
TyG = ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2
hs-CRP
hs-CRP in mg/L
Total Cholesterol (TC)
TC in mmol/l
Tryglicerides (TG)
TG in mmol/l
LDL-Cholesterol (LDL-C)
LDL-C in mmol/l
VLDL-Cholesterol (VLDL-C)
VLDL-C in mmol/l
HDL-Cholesterol (HDL-C)
HDL-Cholesterol (HDL-C)
waist circumferences (WC)
WC in cm
body mass index (BMI)
weight in kg and height in meters will be combined to report BMI in kg/m^2
body fat in percentage
fat content (%) using electronic scales-analyzers of body composition Tanita Scale BC-601
visceral fat content
visceral fat content using electronic scales-analyzers of body composition Tanita Scale BC-601

Full Information

First Posted
March 16, 2023
Last Updated
March 27, 2023
Sponsor
Bogomolets National Medical University
Collaborators
Taras Shevchenko National University of Kyiv, Danylo Halytsky Lviv National Medical University, Kyiv City Clinical Endocrinology Center, Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine, MirImmunoFarm, Stellar Biotics
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1. Study Identification

Unique Protocol Identification Number
NCT05804422
Brief Title
Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Adults NAFLD Patients (DELI_NAFLD Study)
Official Title
Efficacy and Safety of Probiotic Lysate (Postbiotic and Metabiotic) Supplementation in Adults NAFLD Patients
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2023 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
December 31, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Bogomolets National Medical University
Collaborators
Taras Shevchenko National University of Kyiv, Danylo Halytsky Lviv National Medical University, Kyiv City Clinical Endocrinology Center, Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine, MirImmunoFarm, Stellar Biotics

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The current study aim was to conduct placebo-controlled randomize clinical trial to assess the short-term efficacy and safety of postbiotics on hepatic fat content as measured by MRI-PDFF and ultrasonography, transaminases activity, biochemichal hepatic steatosis indeces and chronic systemic inflammatory markers in NAFLD patients. The study will include 3 periods. Screening period of up to 1 weeks to assess the eligibility to inclusion/exclusion criteria. Treatment period for 3 month where the participants will receive a twice daily oral dose of postbiotics (cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023) at the assigned dose of 100mg or placebo in capsules. During this period monthly phone contacts will be done for assessment of compliance and safety concerns. Follow-up period of up to 3 month.
Detailed Description
The scientific literature points to the beneficial properties of probiotics in the process of regulating metabolism, yet at the same time, some scientific papers question the effectiveness and the safety of probiotics. In turn, postbiotics and metabiotics are preparations of inanimate microorganisms and / or their components, which are directly identified with the safety of their use and the health benefits of the host. Due to the chemical structure of postbiotics and metabiotics, it is found that they have many health benefits; in particular, they have a local effect on certain tissues of the intestinal epithelium, and influence on many other organs and tissues. It is postbiotics metabolites and metabiotics structural cell fragments that create the appearance of a therapeutic effect of probiotics, which, in turn, limits the risk of introducing living microorganisms into a weakened immune defence. It should also be pointed out that postbiotics and metabiotics are more stable and have a longer shelf-life. The practical use of probiotics and the study of the mechanism of their action made lately to find that a certain level of biological activity is preserved by dead probiotic cells and even their lysates, which are the natural mixes of metabiotic and postbiotic substances; a biological activity which is strongly oriented toward gut health and immune system regulation. Because probiotic lysates demonstrated biological activity without any of the potential adverse side effects associated with live bacterial cells, one of the future goal is research of the novel postbiotics and metabiotics substances, their individual structures and biological characteristics for understanding their way of communications with host cells and microbiota representatives. Considering the high biological activity and safety of postbiotics and metabiotic substances, it can be concluded that such a treatment vector will be promising in the near future. That's why our investigation will concentrate on postbiotic, a supplement containing dry fermented cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023. Recent scientific animal studies on the stated issues point to the benefits of some postbiotics in treating metabolic disorders. TThe current study aim was to conduct placebo-controlled randomize clinical trial to assess the short-term efficacy and safety of postbiotics on hepatic fat content as measured by MRI-PDFF and ultrasonography, transaminases activity, biochemichal hepatic steatosis indeces and chronic systemic inflammatory markers in NAFLD patients. The study will include 3 periods. Screening period of up to 1 weeks to assess the eligibility to inclusion/exclusion criteria. Treatment period for 3 month where the participants will receive a twice daily oral dose of postbiotics (cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023) at the assigned dose of 100mg or placebo in capsules. All capsules will be identical with similar organoleptic characteristics (e.g., taste and appearance).. Follow-up period of up to 3 month. The pre-randomization period will be 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease, Non Alcoholic Fatty Liver, Hepatic Steatosis, Fatty Liver
Keywords
Postbiotics, metabiotics, L. rhamnosus, L. delbrueckii, Obesity, Non-Alcoholic Fatty Liver Disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Masking Description
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
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Probiotic lysate (postbiotic and metabiotc) group
Arm Type
Active Comparator
Arm Description
oral, 2 capsules per day (BID) for 3 month treatment
Arm Title
Placebo group
Arm Type
Placebo Comparator
Arm Description
placebo, oral, 2 capsules per day (BID) for 3 month treatment
Intervention Type
Dietary Supplement
Intervention Name(s)
Probiotic lysate (postbiotic and metabiotc)
Other Intervention Name(s)
Del-Immune V® Extra
Intervention Description
Each capsule contains 100 mg of cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023 in powder
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
changes in hepatic fat content
Description
will be measured by magnetic resonance proton density fat fraction (MRI-PDFF) in %
Time Frame
at 3 month (end of treatment)
Title
changes in hepatic fat content
Description
will be measured by ultrasound attenuation coefficient measurement (ACM) in dB/cm
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
changes in fatty liver index (FLI)
Description
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
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Secondary Outcome Measure Information:
Title
hepatic steatosis index (HSI)
Description
HSI = 8 x ALT/AST + BMI(+ 2 if type 2 diabetes yes, + 2 if female)
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
ALT
Description
in IU/L
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
AST
Description
AST in IU/L
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
GGT
Description
GGT in IU/L
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
liver stiffness (LS)
Description
liver stiffness (LS) will be measured by Shear Wave Elastography (SWE) and expressed in kPa
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
TyG index
Description
TyG = ln [Fasting triglyceride (mg / dl) x Fasting glucose (mg / dl)] / 2
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
hs-CRP
Description
hs-CRP in mg/L
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
Total Cholesterol (TC)
Description
TC in mmol/l
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
Tryglicerides (TG)
Description
TG in mmol/l
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
LDL-Cholesterol (LDL-C)
Description
LDL-C in mmol/l
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
VLDL-Cholesterol (VLDL-C)
Description
VLDL-C in mmol/l
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
HDL-Cholesterol (HDL-C)
Description
HDL-Cholesterol (HDL-C)
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
waist circumferences (WC)
Description
WC in cm
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
body mass index (BMI)
Description
weight in kg and height in meters will be combined to report BMI in kg/m^2
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
body fat in percentage
Description
fat content (%) using electronic scales-analyzers of body composition Tanita Scale BC-601
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Title
visceral fat content
Description
visceral fat content using electronic scales-analyzers of body composition Tanita Scale BC-601
Time Frame
at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: adult participants (ages 18-70) presence of NAFLD diagnosed 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 MRI-PDFF of at least 6.4%; fatty liver index (FLI) more than 60; BMI 25-39.9 kg/m2; aspartate transaminase (AST) and alanine transaminase (ALT) ≤3x upper limit of normal; written informed consent. Exclusion Criteria: recent hepatitis, or positive screening test for hepatitis B (hepatitis B virus surface antigen) or hepatitis C (hepatitis C antibody); alcohol abuse (>20 g/day (2 standard drinks) in women or > 30 g/d (3 drinks) in men over a two-year period); 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 an agents with gut microbiota modulation activity (antibiotic, pro-, pre-, post or synbiotics supplement etc.) within 3 months prior to enrollment; allergy on probiotics or their components; 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); subjects with a history of bariatric surgery or significant weight loss (> 5% body weight) or rapid weight loss (> 1.6kg/week), within 6 months prior to enrollment; uncontrolled cardiovascular or respiratory disease, decompensated liver disease including ascites, encephalopathy or variceal bleeding, active malignancy, or chronic infections; participant who had severe course of COVID-19 (extracorporeal membrane oxygenation, mechanically ventilated), and/or had a confirmed case of COVID-19 within 4 weeks prior to enrollment; participation in other clinical trials; presence of pregnancy or lactation.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nazarii Kobyliak, Assoc. Prof
Phone
0442356005
Email
nazariikobyliak@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nazarii Kobyliak, PhD
Organizational Affiliation
Bogomolets National Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bogomolets National Medical University
City
Kyiv
ZIP/Postal Code
01601
Country
Ukraine
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nazarii Kobyliak, PhD
Phone
+380442356005
Email
nazariikobyliak@gmail.com
First Name & Middle Initial & Last Name & Degree
Elina Manzhalii, PhD
Facility Name
Kyiv City Clinical Endocrinology Center
City
Kyiv
ZIP/Postal Code
01601
Country
Ukraine
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Dmytro Kyriienko, PhD
Phone
0442356005
Email
kyriienko1954@gmail.com
Facility Name
Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine
City
Kyiv
ZIP/Postal Code
02000
Country
Ukraine
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Olena Baka
Phone
0980985229
Email
olenabaka@yahoo.com
Facility Name
Danylo Halytsky Lviv National Medical University
City
Lviv
ZIP/Postal Code
79010
Country
Ukraine
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Maryana Savytska, PhD
Phone
0442356005
Email
msavytska88@gmail.com

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Adults NAFLD Patients (DELI_NAFLD Study)

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