xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT06032988</url>
    </required_header>
    <id_info>
      <org_study_id>IRB approval No 306/26.04.2021</org_study_id>
      <nct_id>NCT06032988</nct_id>
    </id_info>
    <brief_title>Effect of Probiotic Supplements on Metabolic Control of People With Type 2 Diabetes Mellitus in Greece</brief_title>
    <official_title>The Effect of Probiotic Supplements on Metabolic Control of People With Type 2 Diabetes in Greece. A Randomized, Double-blind, Placebo-controlled Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Konstantinos Makrilakis, MD</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Uni-Pharma</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>National and Kapodistrian University of Athens</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this interventional clinical study is to examine if there will be a change in&#xD;
        metabolic indices (glycemic and lipid parameters) among persons with type 2 diabetes (T2D)&#xD;
        who will receive a probiotic dietary supplement capsule for 6 months compared to those not&#xD;
        receiving such a treatment (they will receive a matching placebo capsule that does not&#xD;
        contain active ingredients).&#xD;
  &#xD;
        The main questions to answer are:&#xD;
  &#xD;
          1. Will glycemic indices, i.e., glycated hemoglobin (HbA1c) and fasting blood glucose, be&#xD;
             different in people taking the probiotic treatment, compared to those not taking it,&#xD;
             after 6 months?&#xD;
  &#xD;
          2. Will other metabolic indices, mostly blood lipid levels (total cholesterol,&#xD;
             triglycerides, HDL- and LDL-cholesterol) and liver function tests, be different in&#xD;
             people taking the probiotic treatment compared to those not taking it after 6 months?&#xD;
  &#xD;
          3. Will adiposity measures (weight, waist circumference) be affected by probiotic treatment&#xD;
             in the two groups? Studies in animals and humans, mostly of shorter duration (&lt;12 weeks)&#xD;
             so far, have shown a possible trend towards improvement with probiotic treatment in all&#xD;
             these parameters, but longer-term studies are scarce, and in Greece, there is none.&#xD;
             Since diabetes treatment is complex (usually involving many medications) and expensive,&#xD;
             developing cost-effective functional healthcare products for regulating blood glucose&#xD;
             more efficiently has been recognized as a beneficial alternative.&#xD;
  &#xD;
        Participants will be adult individuals (&gt;18 years old) with T2D, followed at the outpatient&#xD;
        Diabetes Center of the Laiko General Hospital, National and Kapodistrian University of Athens&#xD;
        Medical School, in Athens, Greece, who will be randomized to receive either a probiotic&#xD;
        dietary supplement or a matching placebo capsule, once a day. They will be followed every 3&#xD;
        months (as is customary for diabetic patients). They will be monitored regarding their&#xD;
        glycemic control (HbA1c and fasting blood glucose), lipid parameters, liver and renal&#xD;
        function, and anthropometric changes (weight, waist circumference, and blood pressure).&#xD;
        Furthermore, participants will be asked to give a stool sample at the study's beginning and&#xD;
        end (6 months) for gut microbiota analysis. A questionnaire will also be administered at the&#xD;
        last visit (6 months) asking about patients' tolerance and satisfaction with the treatment&#xD;
        (frequency of constipation, diarrhea, bowel function, bloating, gas production, and abdominal&#xD;
        pain).&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Eligible participants will be randomized using a computer generator (www.randomization.com),&#xD;
        which randomizes each subject to a single treatment by using the method of randomly permuted&#xD;
        blocks, to receive either a multi-strain probiotic supplement (in the form of a capsule&#xD;
        [LactoLevure^R]) or a matching placebo capsule, once a day. The probiotic capsule contains&#xD;
        the species: Lactobacillus Acidophilus, Lactobacillus plantarum, Bifidobacterium lactis,&#xD;
        Saccharomyces boulardii (in the following quantities of colony-forming units [CFU]:&#xD;
        Lactobacillus Acidophilus 1.75x10^9 CFU, Lactobacillus plantarum 0.5x10^9 CFU,&#xD;
        Bifidobacterium lactis 1.75x10^9 CFU, Saccharomyces boulardii 1.5x10^9 CFU). The capsules&#xD;
        (probiotics brand name LactoLevure^R and placebo) are prepared and donated to the study&#xD;
        personnel by an unrestricted research grant from Uni-Pharma Greece, the producer of&#xD;
        LactoLevure^R (Uni-Pharma Pharmaceutical Laboratories S.A., Kifisia, Greece), who will have&#xD;
        no other interference with the planning, the conduction, or the analysis of the results of&#xD;
        the study. The probiotic and placebo capsules will have an identical appearance and&#xD;
        packaging. Neither the participants nor the investigators will be aware of the treatment&#xD;
        assignments in this double-blinded study. Additionally, participants will be asked not to&#xD;
        change their diet and exercise habits and to refrain from consuming yoghurt or other similar&#xD;
        dietary supplements during the study. Care will be taken not to change the other&#xD;
        pharmaceutical medicines during the study (participants who will have to initiate insulin&#xD;
        treatment will be excluded from further follow-up and analysis in the study).&#xD;
  &#xD;
        Sample size calculation will be based on previous similar studies considering 80% power at α&#xD;
        = 0.05 to detect a difference in metabolic indices. All participants will be given verbal and&#xD;
        written information about the study and will sign an informed consent form according to the&#xD;
        recommendations of the Declaration of Helsinki.&#xD;
  &#xD;
        Participants will be seen every 3 months in the outpatient Diabetes center of the Laiko&#xD;
        General Hospital, National and Kapodistrian University of Athens Medical School, in Athens,&#xD;
        Greece (as is customary for diabetic patients) and will be monitored regarding their glycemic&#xD;
        control (HbA1c and fasting blood glucose), lipid parameters, liver and renal function, and&#xD;
        anthropometric variables changes (weight and waist circumference, blood pressure).&#xD;
        Furthermore, participants will be asked to give a stool sample at the study's beginning and&#xD;
        end (6 months) for gut microbiota analysis. A questionnaire will also be administered at the&#xD;
        last visit (6 months) asking about patients' tolerance and satisfaction with the treatment&#xD;
        (frequency of constipation, diarrhea, bowel function, bloating, gas production, and abdominal&#xD;
        pain).&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Enrolling by invitation</overall_status>
    <start_date type="Actual">August 23, 2023</start_date>
    <completion_date type="Anticipated">March 2024</completion_date>
    <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>The present study will be a single-center, randomized, double-blind, placebo-controlled trial of a 6-month duration involving persons with T2D. Participants will receive either a multi-strain probiotic supplement (in the form of a capsule) or a matching placebo capsule once a day.</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
      <masking_description>Participants will be randomly assigned (using a computer generator [www.randomization.com], which randomizes each subject to a single treatment using randomly permuted blocks) to receive probiotic or placebo treatment, blinded to participants, study investigators, and physicians caring for the patients.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Effects of probiotics supplementation on glycemic control (HbA1c)</measure>
      <time_frame>6 months</time_frame>
      <description>To measure the difference of the change from baseline in mean HbA1c (percentage points) between the intervention (probiotic) group and placebo, after 6 months</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Effects of probiotics supplementation on fasting blood glucose (FBG)</measure>
      <time_frame>6 months</time_frame>
      <description>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</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of probiotics supplementation on lipid parameters (Total cholesterol, Triglycerides, HDL-C, LDL-C)</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of probiotics supplementation on liver function tests (AST, ALT, γGT, Alkaline Phosphatase)</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of probiotics supplementation on adiposity measures (BMI, Waist circumference)</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Effects of probiotics supplementation on changes in gut microbiota diversity (alpha- and beta-diversity)</measure>
      <time_frame>6 months</time_frame>
      <description>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.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">90</enrollment>
    <condition>Diabetes Mellitus, Type 2</condition>
    <arm_group>
      <arm_group_label>LactoLevure</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>The probiotic capsule LactoLevure^R will be given once a day</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Placebo capsules will consist of identical to the LactoLevure^R capsules of powdered glucose polymer, and will be given once a day</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>LactoLevure</intervention_name>
      <description>Participants will receive LactoLevure^R probiotic dietary supplement or matching placebo once a day.</description>
      <arm_group_label>LactoLevure</arm_group_label>
      <arm_group_label>Placebo</arm_group_label>
      <other_name>Probiotic</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  T2D diagnosis of &gt;6 months' duration&#xD;
  &#xD;
            -  Age 18-90 years&#xD;
  &#xD;
            -  A body-mass index (BMI) &gt;18.5 kg/m^2&#xD;
  &#xD;
            -  HbA1c level &gt;6 percent (%)&#xD;
  &#xD;
            -  on stable antidiabetic medications (oral or injectable glucagon-like peptide 1&#xD;
               receptor agonists [GLP-1 RAs]) for 8 weeks before the screening&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Type 1 or other type of diabetes&#xD;
  &#xD;
            -  Pregnancy or wishing to become pregnant during the study&#xD;
  &#xD;
            -  End-stage kidney failure on dialysis, presence of other diseases, including cancer or&#xD;
               severe hepatic insufficiency (transaminases &gt;3.5x above normal)&#xD;
  &#xD;
            -  The use of other probiotic products or antibiotics over the previous 6 months&#xD;
  &#xD;
            -  Participation in other clinical trials&#xD;
  &#xD;
            -  Insulin administration&#xD;
  &#xD;
            -  The presence of other medical conditions that in the opinion of the investigators&#xD;
               could jeopardize compliance with the protocol (e.g., malabsorption syndrome or an&#xD;
               inability to take orally administered medications)&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>90 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>KONSTANTINOS MAKRILAKIS, MD, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>National and Kapodistrian University of Athens</affiliation>
    </overall_official>
    <location>
      <facility>
        <name>Laiko General Hospital</name>
        <address>
          <city>Athens</city>
          <state>Attica</state>
          <zip>11526</zip>
          <country>Greece</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>Greece</country>
    </location_countries>
    <reference>
      <citation>Bock PM, Telo GH, Ramalho R, Sbaraini M, Leivas G, Martins AF, Schaan BD. The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2021 Jan;64(1):26-41. doi: 10.1007/s00125-020-05295-1. Epub 2020 Oct 13.</citation>
      <PMID>33047170</PMID>
    </reference>
    <reference>
      <citation>Rittiphairoj T, Pongpirul K, Janchot K, Mueller NT, Li T. Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Adv Nutr. 2021 Jun 1;12(3):722-734. doi: 10.1093/advances/nmaa133.</citation>
      <PMID>33126241</PMID>
    </reference>
    <reference>
      <citation>Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: Where are we now? Diabetes Res Clin Pract. 2018 Dec;146:111-118. doi: 10.1016/j.diabres.2018.10.008. Epub 2018 Oct 18.</citation>
      <PMID>30342053</PMID>
    </reference>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 27, 2023</study_first_submitted>
    <study_first_submitted_qc>September 4, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 2023</study_first_posted>
    <last_update_submitted>September 4, 2023</last_update_submitted>
    <last_update_submitted_qc>September 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>National and Kapodistrian University of Athens</investigator_affiliation>
      <investigator_full_name>Konstantinos Makrilakis, MD</investigator_full_name>
      <investigator_title>Professor of Internal Medicine</investigator_title>
    </responsible_party>
    <keyword>Diabetes mellitus type 2</keyword>
    <keyword>Probiotics</keyword>
    <keyword>Gut microbiota</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Diabetes Mellitus</mesh_term>
      <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>Individual participants' data will be deposited anonymized in &quot;Pergamos&quot;, the central Institutional Repository of the National and Kapodistrian University of Athens</ipd_description>
      <ipd_time_frame>Within six months of completion of the study</ipd_time_frame>
      <ipd_access_criteria>Anyone who wishes to access the data</ipd_access_criteria>
      <ipd_url>https://pergamos.lib.uoa.gr/uoa/dl/frontend/en/index.html</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT06032988
  org study id: IRB approval No 306/26.04.2021
  nct id: NCT06032988
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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).
  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).
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: The present study will be a single-center, randomized, double-blind, placebo-controlled trial of a 6-month duration involving persons with T2D. Participants will receive either a multi-strain probiotic supplement (in the form of a capsule) or a matching placebo capsule once a day.
  primary purpose: Treatment
  masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  masking description: Participants will be randomly assigned (using a computer generator [www.randomization.com], which randomizes each subject to a single treatment using randomly permuted blocks) to receive probiotic or placebo treatment, blinded to participants, study investigators, and physicians caring for the patients.
  measure: Effects of probiotics supplementation on glycemic control (HbA1c)
  time frame: 6 months
  description: To measure the difference of the change from baseline in mean HbA1c (percentage points) between the intervention (probiotic) group and placebo, after 6 months
  measure: Effects of probiotics supplementation on fasting blood glucose (FBG)
  time frame: 6 months
  description: 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
  measure: Effects of probiotics supplementation on lipid parameters (Total cholesterol, Triglycerides, HDL-C, LDL-C)
  time frame: 6 months
  description: 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.
  measure: Effects of probiotics supplementation on liver function tests (AST, ALT, γGT, Alkaline Phosphatase)
  time frame: 6 months
  description: 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.
  measure: Effects of probiotics supplementation on adiposity measures (BMI, Waist circumference)
  time frame: 6 months
  description: 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.
  measure: Effects of probiotics supplementation on changes in gut microbiota diversity (alpha- and beta-diversity)
  time frame: 6 months
  description: 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.
  arm group label: LactoLevure
  arm group type: Active Comparator
  description: The probiotic capsule LactoLevure^R will be given once a day
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Placebo capsules will consist of identical to the LactoLevure^R capsules of powdered glucose polymer, and will be given once a day
  intervention type: Dietary Supplement
  intervention name: LactoLevure
  description: Participants will receive LactoLevure^R probiotic dietary supplement or matching placebo once a day.
  arm group label: LactoLevure
  arm group label: Placebo
  other name: Probiotic
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 90 Years
  healthy volunteers: No
  last name: KONSTANTINOS MAKRILAKIS, MD, PhD
  role: Principal Investigator
  affiliation: National and Kapodistrian University of Athens
  facility: 
  country: Greece
  citation: Bock PM, Telo GH, Ramalho R, Sbaraini M, Leivas G, Martins AF, Schaan BD. The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in individuals with diabetes: a systematic review and meta-analysis. Diabetologia. 2021 Jan;64(1):26-41. doi: 10.1007/s00125-020-05295-1. Epub 2020 Oct 13.
  PMID: 33047170
  citation: Rittiphairoj T, Pongpirul K, Janchot K, Mueller NT, Li T. Probiotics Contribute to Glycemic Control in Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Adv Nutr. 2021 Jun 1;12(3):722-734. doi: 10.1093/advances/nmaa133.
  PMID: 33126241
  citation: Vallianou NG, Stratigou T, Tsagarakis S. Microbiome and diabetes: Where are we now? Diabetes Res Clin Pract. 2018 Dec;146:111-118. doi: 10.1016/j.diabres.2018.10.008. Epub 2018 Oct 18.
  PMID: 30342053
  responsible party type: Sponsor-Investigator
  investigator affiliation: National and Kapodistrian University of Athens
  investigator full name: Konstantinos Makrilakis, MD
  investigator title: Professor of Internal Medicine
  mesh term: Diabetes Mellitus
  mesh term: Diabetes Mellitus, Type 2
  sharing ipd: Yes
  ipd description: Individual participants' data will be deposited anonymized in "Pergamos", the central Institutional Repository of the National and Kapodistrian University of Athens
  ipd time frame: Within six months of completion of the study
  ipd access criteria: Anyone who wishes to access the data
  ipd url: https://pergamos.lib.uoa.gr/uoa/dl/frontend/en/index.html