Postbiotics Supplementation for Type 2 Diabetes Patients (DELI_Diab Study)

Sponsor

Bogomolets National Medical University (Other)

Overall Status

Recruiting

CT.gov ID

NCT05770076

Collaborator

Taras Shevchenko National University of Kyiv (Other), Danylo Halytsky Lviv National Medical University (Other), Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine (Other), Kyiv City Clinical Endocrinology Center (Other)

Enrollment

Locations

Arms

10.9

Anticipated Duration (Months)

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

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 as an adjunction to the standard anti-diabetic therapy on insulin resistance, glycemic control parameters, β-cells functional activity, anthropometric parameters and markers of a chronic systemic inflammatory response in type 2 diabetes 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.

Condition or Disease	Intervention/Treatment	Phase
Obesity Obesity, Abdominal Insulin Resistance Insulin Sensitivity Type2 Diabetes Type 2 Diabetes Mellitus in Obese	Dietary Supplement: Postbiotic Dietary Supplement: Placebo	N/A

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. The current study aim was to conduct placebo-controlled randomize clinical trial to assess the short-term efficacy and safety of postbiotics as an adjunction to the standard anti-diabetic therapy on insulin resistance, glycemic control parameters, β-cells functional activity, anthropometric parameters and markers of a chronic systemic inflammatory response in type 2 diabetes 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

60 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes 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

Primary Purpose:

Treatment

Official Title:

Effect of Postbiotics Supplementation on Metabolic Parameters in Type 2 Diabetes Patients

Actual Study Start Date :

Feb 1, 2023

Anticipated Primary Completion Date :

Dec 31, 2023

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Postbiotic group postbiotic, oral, 2 capsules per day (BID) for 3 month treatment	Dietary Supplement: Postbiotic Each postbiotic capsule contains 100 mg of cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023 in powder Other Names: Del-Immune Extra V®
Placebo Comparator: Placebo group placebo, oral, 2 capsules per day (BID) for 3 month treatment	Dietary Supplement: Placebo Placebo

Arm

Intervention/Treatment

Active Comparator: Postbiotic group

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

Dietary Supplement: Postbiotic

Each postbiotic capsule contains 100 mg of cell lysate and DNA fragments of the probiotic strain L. rhamnosus DV - NRRLB-68023 in powder

Other Names:

Del-Immune Extra V®

Placebo Comparator: Placebo group

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

Dietary Supplement: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

Changes in HbA1c level [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
HbA1c in %
Changes in fasting plasma glucose (FPG) level [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
FPG in mmol/L

Secondary Outcome Measures

HOMA-2IR [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php
insulin sensitivity (%S) [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php [Time Frame: 8 weeks compared to baseline]
β-cell function (%B) [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
This model can be calculated using the software supplied by the Oxford Centre for Diabetes Endocrinology and Metabolism available at http://www.dtu.ox.ac.uk/homacalculator/index.php [Time Frame: 8 weeks compared to baseline]
C-peptide [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
C-peptide, ng/ml
High censitivity CRP (C-reactive Protein) [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
hs-CRP in mg/L
weight [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
weight in kg
waist circumferences (WC) [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
WC in cm
body mass index (BMI) [at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline]
weight in kg and height in meters will be combined to report BMI in kg/m^2

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adult participants (ages 18-70)
presence of T2D diagnosed according to criteria of the American Diabetes Association;
BMI 25-40 kg/m2;
patient who treated with diet and exercise alone or metformin, SUs and insulin on a stabilized dose for at least 3 months before the study;
daily insulin dosage less than 60IU;
HbA1c between 6.5 and 10.0 %;
written informed consent.

Exclusion Criteria:

presence of type 1 diabetes;
severe diabetes-related complications at screening (ie, end-stage DKD, neuropathy requiring pharmacological treatment, proliferative retinopathy, autonomic neuropathy);
treatment with other than mention in inclusion criteria antidiabetic drugs (pioglitazone, SGLT-2 antagonists, GLP-1 analogues, DPP IV inhibitors etc);
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;
presence of gastrointestinal diseases such as food allergy, celiac disease, non-specific ulcerative colitis;
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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Bogomolets National Medical University	Kyiv	Ukraine	01601
2	Kyiv City Clinical Endocrinology Center	Kyiv	Ukraine	01601
3	Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine	Kyiv	Ukraine	02000
4	Danylo Halytsky Lviv National Medical University	Lviv	Ukraine	79010

Sponsors and Collaborators

Bogomolets National Medical University
Taras Shevchenko National University of Kyiv
Danylo Halytsky Lviv National Medical University
Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine
Kyiv City Clinical Endocrinology Center