Clinical trial NCT05770076: Probiotic Lysate (Postbiotic and Metabiotic) Supplementation for Type 2 Diabetes Patients (DELI_Diab Study)
Official title: Effect of Probiotic Lysate (Postbiotic and Metabiotic) Supplementation on Metabolic Parameters in Type 2 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Obesity, Abdominal
Insulin Resistance
Insulin Sensitivity
Type2 Diabetes
Type 2 Diabetes Mellitus in Obese
Keywords: Postbiotics
metabiotics
L. rhamnosus
L. delbrueckii
Obesity
Type2 Diabetes
Insulin Resistance
Lead sponsor: Bogomolets National Medical University
Sponsor class: OTHER
Collaborators: name: Taras Shevchenko National University of Kyiv
name: Danylo Halytsky Lviv National Medical University
name: Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine
name: Kyiv City Clinical Endocrinology Center
name: MirImmunoFarm
name: Stellar Biotics
First posted: 2023-03-15
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Changes in HbA1c level
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: Changes in fasting plasma glucose (FPG) level
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Secondary outcomes:
measure: HOMA-2IR
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: insulin sensitivity (%S)
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: β-cell function (%B)
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: C-peptide
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: High censitivity CRP (C-reactive Protein)
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: weight
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: waist circumferences (WC)
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
measure: body mass index (BMI)
timeFrame: at 3 month (end of treatment) and 6 month (follow-up period) compared to baseline
Other outcomes:
Locations:
city: Kyiv
country: Ukraine
facility: Bogomolets National Medical University
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Endocrinology Center
city: Kyiv
country: Ukraine
facility: Center for Innovative Medical Technologies of the National Academy of Sciences of Ukraine
city: Lviv
country: Ukraine
facility: Danylo Halytsky Lviv National Medical University
Study officials:
affiliation: Bogomolets National Medical University
name: Nazarii Kobyliak, PhD
role: PRINCIPAL_INVESTIGATOR
References: