Effect of Probiotic Supplements on Metabolic Control of People With Type 2 Diabetes Mellitus in Greece

May 26, 2025 updated by: Konstantinos Makrilakis, MD

The Effect of Probiotic Supplements on Metabolic Control of People With Type 2 Diabetes in Greece. A Randomized, Double-blind, Placebo-controlled Study

The goal of this interventional clinical study is to examine if there will be a change in metabolic indices (glycemic and lipid parameters) among persons with type 2 diabetes (T2D) who will receive a probiotic dietary supplement capsule for 6 months compared to those not receiving such a treatment (they will receive a matching placebo capsule that does not contain active ingredients).

The main questions to answer are:

  1. Will glycemic indices, i.e., glycated hemoglobin (HbA1c) and fasting blood glucose, be different in people taking the probiotic treatment, compared to those not taking it, after 6 months?
  2. Will other metabolic indices, mostly blood lipid levels (total cholesterol, triglycerides, HDL- and LDL-cholesterol) and liver function tests, be different in people taking the probiotic treatment compared to those not taking it after 6 months?
  3. Will adiposity measures (weight, waist circumference) be affected by probiotic treatment in the two groups? Studies in animals and humans, mostly of shorter duration (<12 weeks) so far, have shown a possible trend towards improvement with probiotic treatment in all these parameters, but longer-term studies are scarce, and in Greece, there is none. Since diabetes treatment is complex (usually involving many medications) and expensive, developing cost-effective functional healthcare products for regulating blood glucose more efficiently has been recognized as a beneficial alternative.

Participants will be adult individuals (>18 years old) with T2D, followed at the outpatient Diabetes Center of the Laiko General Hospital, National and Kapodistrian University of Athens Medical School, in Athens, Greece, who will be randomized to receive either a probiotic dietary supplement or a matching placebo capsule, once a day. They will be followed every 3 months (as is customary for diabetic patients). They will be monitored regarding their glycemic control (HbA1c and fasting blood glucose), lipid parameters, liver and renal function, and anthropometric changes (weight, waist circumference, and blood pressure). Furthermore, participants will be asked to give a stool sample at the study's beginning and end (6 months) for gut microbiota analysis. A questionnaire will also be administered at the last visit (6 months) asking about patients' tolerance and satisfaction with the treatment (frequency of constipation, diarrhea, bowel function, bloating, gas production, and abdominal pain).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Eligible participants will be randomized using a computer generator (www.randomization.com), which randomizes each subject to a single treatment by using the method of randomly permuted blocks, to receive either a multi-strain probiotic supplement (in the form of a capsule [LactoLevure^R]) or a matching placebo capsule, once a day. The probiotic capsule contains the species: Lactobacillus Acidophilus, Lactobacillus plantarum, Bifidobacterium lactis, Saccharomyces boulardii (in the following quantities of colony-forming units [CFU]: Lactobacillus Acidophilus 1.75x10^9 CFU, Lactobacillus plantarum 0.5x10^9 CFU, Bifidobacterium lactis 1.75x10^9 CFU, Saccharomyces boulardii 1.5x10^9 CFU). The capsules (probiotics brand name LactoLevure^R and placebo) are prepared and donated to the study personnel by an unrestricted research grant from Uni-Pharma Greece, the producer of LactoLevure^R (Uni-Pharma Pharmaceutical Laboratories S.A., Kifisia, Greece), who will have no other interference with the planning, the conduction, or the analysis of the results of the study. The probiotic and placebo capsules will have an identical appearance and packaging. Neither the participants nor the investigators will be aware of the treatment assignments in this double-blinded study. Additionally, participants will be asked not to change their diet and exercise habits and to refrain from consuming yoghurt or other similar dietary supplements during the study. Care will be taken not to change the other pharmaceutical medicines during the study (participants who will have to initiate insulin treatment will be excluded from further follow-up and analysis in the study).

Sample size calculation will be based on previous similar studies considering 80% power at α = 0.05 to detect a difference in metabolic indices. All participants will be given verbal and written information about the study and will sign an informed consent form according to the recommendations of the Declaration of Helsinki.

Participants will be seen every 3 months in the outpatient Diabetes center of the Laiko General Hospital, National and Kapodistrian University of Athens Medical School, in Athens, Greece (as is customary for diabetic patients) and will be monitored regarding their glycemic control (HbA1c and fasting blood glucose), lipid parameters, liver and renal function, and anthropometric variables changes (weight and waist circumference, blood pressure). Furthermore, participants will be asked to give a stool sample at the study's beginning and end (6 months) for gut microbiota analysis. A questionnaire will also be administered at the last visit (6 months) asking about patients' tolerance and satisfaction with the treatment (frequency of constipation, diarrhea, bowel function, bloating, gas production, and abdominal pain).

Study Type

Interventional

Enrollment (Actual)

90

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Greece
    • Attica
      • Athens, Attica, Greece, 11526
        • Laiko General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • T2D diagnosis of >6 months' duration
  • Age 18-90 years
  • A body-mass index (BMI) >18.5 kg/m^2
  • HbA1c level >6 percent (%)
  • on stable antidiabetic medications (oral or injectable glucagon-like peptide 1 receptor agonists [GLP-1 RAs]) for 8 weeks before the screening

Exclusion Criteria:

  • Type 1 or other type of diabetes
  • Pregnancy or wishing to become pregnant during the study
  • End-stage kidney failure on dialysis, presence of other diseases, including cancer or severe hepatic insufficiency (transaminases >3.5x above normal)
  • The use of other probiotic products or antibiotics over the previous 6 months
  • Participation in other clinical trials
  • Insulin administration
  • The presence of other medical conditions that in the opinion of the investigators could jeopardize compliance with the protocol (e.g., malabsorption syndrome or an inability to take orally administered medications)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: LactoLevure
The probiotic capsule LactoLevure^R will be given once a day
Dietary supplement: LactoLevure
Participants will receive LactoLevure^R probiotic dietary supplement or matching placebo once a day.
Other Names:
  • Probiotic
Placebo Comparator: Placebo
Placebo capsules will consist of identical to the LactoLevure^R capsules of powdered glucose polymer, and will be given once a day
Dietary supplement: LactoLevure
Participants will receive LactoLevure^R probiotic dietary supplement or matching placebo once a day.
Other Names:
  • Probiotic

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of probiotics supplementation on glycemic control (HbA1c)
Time Frame: 6 months
To measure the difference of the change from baseline in mean HbA1c (percentage points) between the intervention (probiotic) group and placebo, after 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effects of probiotics supplementation on fasting blood glucose (FBG)
Time Frame: 6 months
To measure the difference of the change from baseline of mean fasting blood glucose (FBG, mg/dl) between the intervention (probiotic) group and placebo, after 6 months
6 months
Effects of probiotics supplementation on lipid parameters (Total cholesterol, Triglycerides, HDL-C, LDL-C)
Time Frame: 6 months
To measure the difference of the change from baseline of mean blood lipid levels, i.e. total cholesterol (mg/dl), triglycerides (mg/dl), HDL-cholesterol (mg/dl), LDL-cholesterol (mg/dl) between the intervention (probiotic) group and placebo, after 6 months. Any of these blood lipid measurements changes will be reported as lipid effects of the intervention.
6 months
Effects of probiotics supplementation on liver function tests (AST, ALT, γGT, Alkaline Phosphatase)
Time Frame: 6 months
To measure the changes from baseline of mean blood liver function tests, i.e. AST (U/L), ALT (U/L), γGT (U/L) and Alkaline Phosphatase (U/L) between the intervention (probiotic) group and placebo, after 6 months. Any of these liver function test measurements changes will be reported as liver effects of the intervention.
6 months
Effects of probiotics supplementation on adiposity measures (BMI, Waist circumference)
Time Frame: 6 months
To measure the difference of changes from baseline in adiposity characterisitcs (mean body mass index [BMI, kg/m^2] and/or mean waist circumference [cm]) between the intervention (probiotic) and placebo group after 6 months. Either or both of these adiposity measures changes will be reported as adiposity effects of the intervention.
6 months
Effects of probiotics supplementation on changes in gut microbiota diversity (alpha- and beta-diversity)
Time Frame: 6 months
To measure the changes from baseline in stool microbial DNA diversity analyzed through 16S rRNA sequencing between the intervention (probiotic) and placebo group after 6 months. Alpha-diversity will measure the within-group changes in the richness (number) or distribution (evenness) of the microbial sample (in the intervention and the placebo group), whereas beta-diversity will measure the between-groups difference.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Konstantinos Makrilakis, MD

Collaborators

Uni-Pharma

Investigators

  • Principal Investigator: Konstantinos Makrilakis, MD, PhD, National and Kapodistrian University of Athens

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 23, 2023

Primary Completion (Actual)

September 2, 2023

Study Completion (Actual)

September 2, 2023

Study Registration Dates

First Submitted

August 27, 2023

First Submitted That Met QC Criteria

September 4, 2023

First Posted (Actual)

September 13, 2023

Study Record Updates

Last Update Posted (Actual)

May 30, 2025

Last Update Submitted That Met QC Criteria

May 26, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB approval No 306/26.04.2021

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Individual participants' data will be deposited anonymized in "Pergamos", the central Institutional Repository of the National and Kapodistrian University of Athens

IPD Sharing Time Frame

Within six months of completion of the study

IPD Sharing Access Criteria

Anyone who wishes to access the data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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