Clinical trial NCT05765292: Probiotic Supplementation and Pancreatic β-Cell Function in Type 2 Diabetes
Official title: Efficacy and Safety of Multi-strain Probiotic on Pancreatic β-cell Function in Type 2 Diabetes Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type2 Diabetes
Obesity
Insulin Resistance
Obesity, Abdominal
Keywords: probiotics; type 2 diabetes; pancreatic β-cells
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: Kyiv City Clinical Endocrinology Center
First posted: 2023-03-13
Enrollment: 68
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: Probiotics have beneficial effect on obesity related disorders in animal models. Current understanding for the beneficial effects of probiotics in type 2 diabetes strictly relies on animal and clinical data, which mainly focus on their impact on insulin resistance, anthropometric parameters, glycemic control and markers of chronic systemic inflammation. From the other hand, there is a lack of evidence-based probiotic efficacy on pancreatic β-cell function in terms of type 2 diabetes and related metabolic disorders. In this double-blind single center randomized clinical trial, effect of alive multistrain probiotic vs. placebo on pancreatic β-cell function in type 2 diabetes patient will be assessed.

Detailed description: In this single-center double blind, placebo controlled, parallel group study, type 2 diabetes patients from the Kyiv City Clinical Endocrinology Center will be selected. They will be randomly assigned to receive multiprobiotic "Symbiter" or placebo for 8-weeks administered as a sachet formulation in double-blind treatment. Randomization will be done by the study statistician based on a computer-generated list. The groups will be homogeneous according to age, sex and diagnostic criteria. The assignment of groups will be 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 multiprobiotic "Symbiter" will be supplied by Scientific and Production Company "O.D. Prolisok". It contains of 14 alive probiotic strains of 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 and placebo per day. All sachets were identical with similar organoleptic characteristics (e.g., taste and appearance).

The pre-randomization period 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 will be instructed in one-on-one sessions with a dietitian to follow a therapeutic lifestyle-change diet as classiﬁed by the NCEP. In addition, participants will be instructed to continue with stable anti-hyperglycemic treatment and received standardized mild physical training for 1 hour per day.

Patients who underwent study will be instructed to take the trial medication as prescribed. Throughout the study, weekly phone follow-up visits will be provided for assessment of compliance, adherence to the protocol, as well as the recording of adverse events. The effectiveness of therapy will be compared and evaluated separately in the two groups.

Eligibility criteria: Inclusion Criteria:

* adult participants (aged 18 to 75);
* presence of T2D diagnosis based on the criteria of the American Diabetes Association (plasma glucose in fasting state ≥7.0 mmol/l; plasma glucose at random measuring ≥11.1 mmol/l; HbA1c ≥6.5% or glucose \> 11.1 mmol/l 2 hours after tolerance test with 75 g of glucose);
* presence of pancreatic β-cell dysfunction which defined as HOMA2-β\<50%;
* treatment with insulin therapy alone or in combination with oral anti-diabetic drugs (metformin and/or sulphonylureas) in a stable dose for at least 3 months prior to randomization;
* HbA1c level 6.5 to 11.0%;
* signed informed consent

Exclusion Criteria:

* presence of T1D;
* intake of anti-diabetic drugs except for those specified in the inclusion criteria (pioglitazone, glucagon-like peptide (GLP-1) analogs, dipeptide-peptidase 4 (DPP-4) inhibitors, etc.);
* severe diabetes-related complications at screening (ie, end-stage diabetic kidney disease, neuropathy requiring pharmacological treatment, proliferative retinopathy, autonomic neuropathy);
* regular intake of probiotics, prebiotics or antibiotics for 3 months prior the inclusion;
* previously diagnosed allergy to probiotics;
* gastrointestinal disorders including food allergy, gluten-sensitive enteropathy, ulcerative colitis;
* an uncontrolled cardiovascular or respiratory disease, an active malignant tumor 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 another clinical trial;
* pregnancy or lactation.

Primary outcomes:
measure: β-cell function (%B)
timeFrame: 8 weeks compared to baseline
measure: C-peptide
timeFrame: 8 weeks compared to baseline
Secondary outcomes:
measure: HOMA-2IR
timeFrame: 8 weeks compared to baseline
measure: insulin sensitivity (%S)
timeFrame: 8 weeks compared to baseline
measure: HbA1c
timeFrame: 8 weeks compared to baseline
measure: fasting plasma glucose (FPG)
timeFrame: 8 weeks compared to baseline
measure: weight
timeFrame: 8 weeks compared to baseline
measure: waist circumferences (WC)
timeFrame: 8 weeks compared to baseline
measure: body mass index (BMI)
timeFrame: 8 weeks compared to baseline
measure: cytokines levels
timeFrame: 8 weeks 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: Taras Shevchenko National University of Kyiv
city: Lviv
country: Ukraine
facility: Danylo Halytsky Lviv National Medical University
Study officials:
affiliation: Bogomolets National Medical University
name: Nazarii Kobyliak
role: PRINCIPAL_INVESTIGATOR
References: