<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/NCT03032354</url>
  </required_header>
  <id_info>
    <org_study_id>AgaLidka</org_study_id>
    <nct_id>NCT03032354</nct_id>
  </id_info>
  <brief_title>Probiotics in Newly Recognized Type 1 Diabetes</brief_title>
  <official_title>Effect of Lactobacillus Rhamnosus GG and Bifidobacterium Lactis BB 12 on Beta-cell Function in Children With Newly Diagnosed Type 1 Diabetes - a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of Warsaw</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of Warsaw</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>
      They are major genera of bacteria that make up the colon flora in human, constitute&#xD;
      intestinal microbial homeostasis, inhibit growth of pathogens, improve the gut mucosal&#xD;
      barrier and modulate local and systemic immune responses. Changes in gut microbiota can&#xD;
      influence the immune system by increasing gut permeability, intestinal inflammation, and&#xD;
      impaired oral tolerance in type 1 diabetes.Taken together, the data imply that&#xD;
      bacteriotherapy may potentially be used as a tool to modulate the immune system for&#xD;
      preventing islet destruction. Supplementation of Lactobacillus rhamnosus GG and&#xD;
      Bifidobacterium lactis BB12 improved blood glucose control in normoglycaemic pregnant women&#xD;
      and reduced the frequency of gestational diabetes mellitus&#xD;
&#xD;
      Aim of the study:&#xD;
&#xD;
      The effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 on beta-cell&#xD;
      function in children with newly diagnosed type 1 diabetes: a randomized, double blind,&#xD;
      placebo-controlled trial.&#xD;
&#xD;
      Primary end point:&#xD;
&#xD;
      Area under the curve (AUC) of c-peptide level during during fasting and at 30,60,90,120 min&#xD;
      following the start of the meal&#xD;
&#xD;
      Intervention:&#xD;
&#xD;
      Included patients will be randomly assigned to receive a combination of Lactobacillus&#xD;
      rhamnosus GG and Bifidobacterium lactis BB12 (Probiotics Group ) or placebo (Placebo Group )&#xD;
      during six months.&#xD;
&#xD;
      The expected results:&#xD;
&#xD;
      Beneficial effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 on beta-cell&#xD;
      function shown in the properly performed, methodologically accurate study would create a&#xD;
      rationale for its routine use in patients with newly diagnosed type 1 diabetes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Intervention:&#xD;
&#xD;
      At the 6-month follow-up visit will be evaluated adherence and occurrence of side effects of&#xD;
      the study procedure. The outcome measures will be assessed at the beginning of the study, and&#xD;
      at the 6 and 12-month follow-up visit.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">July 15, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</primary_completion_date>
  <phase>Phase 4</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Area under the curve (AUC) during fasting and at 30,60,90,120 min following the start of the meal</measure>
    <time_frame>120 min responses to a mixed meal</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Insulin requirement (U / kg body mass )</measure>
    <time_frame>up 60 days from diabetes recognition, at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>HbA1c</measure>
    <time_frame>up to 60 days from diabetes recognition, at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Weight in kilograms</measure>
    <time_frame>up to 60 days from diabetes recognition, and at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of participants with abnormal laboratory values and/or adverse events that are related to treatment ( eg.abdominal pain, diarrhea , constipation , vomiting,flatulence)</measure>
    <time_frame>at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Occurrence of other autoimmune diseases</measure>
    <time_frame>at 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Height in meters</measure>
    <time_frame>up to 60 days from diabetes recognition, and at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI in kg/m2</measure>
    <time_frame>up to 60 days from diabetes recognition, and at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>BMI score</measure>
    <time_frame>up to 60 days from diabetes recognition, and at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severe hypoglycemia</measure>
    <time_frame>up to 60 days from diabetes recognition, at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ketoacidosis</measure>
    <time_frame>up to 60 days from diabetes recognition, at 3th, 6th, 12th month</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fasting c- peptide concentrations in ng/ml</measure>
    <time_frame>up to 60 days from diabetes recognition, and in: 6th, 12th month</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Diabetes Mellitus, Type 1</condition>
  <arm_group>
    <arm_group_label>Probiotics arm: Probiotics group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>combination of probiotics: Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 in the same capsule</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo arm: Placebo group</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Placebo - maltodextrin</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12</intervention_name>
    <description>Combination therapy of probiotics during 6 months</description>
    <arm_group_label>Probiotics arm: Probiotics group</arm_group_label>
    <other_name>Probiotics</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo, (Placebo group)</intervention_name>
    <description>Placebo during 6 months</description>
    <arm_group_label>Placebo arm: Placebo group</arm_group_label>
    <other_name>Maltodextrin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Type 1 diabetes confirmed by clinical history and the presence of at least one&#xD;
             positive autoantibody: anti-glutamic acid decarboxylase (anti-GAD), islet antigen 2&#xD;
             (IA2), islet cell antibody ( ICA)&#xD;
&#xD;
          -  Fasting c-peptide level &gt;/= 0.4 ng/ml&#xD;
&#xD;
          -  The diagnosis of diabetes during the last 60 days&#xD;
&#xD;
          -  Consent to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Antibiotic-therapy during last 4 weeks&#xD;
&#xD;
          -  Taking of probiotics during last 2 weeks&#xD;
&#xD;
          -  Intestinal infection during last 2 weeks&#xD;
&#xD;
          -  Intestinal chronic diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>17 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Agnieszka Szypowska, Assoc. Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of Warsaw</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Agnieszka Szypowska, Assoc. Prof.</last_name>
    <phone>+48 509928617</phone>
    <email>agnieszka.szypowska@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lidia Groele, PhD</last_name>
    <phone>+48 608 671 083</phone>
    <email>lgroele@wp.pl</email>
  </overall_contact_backup>
  <reference>
    <citation>Kriegel MA, Sefik E, Hill JA, Wu HJ, Benoist C, Mathis D. Naturally transmitted segmented filamentous bacteria segregate with diabetes protection in nonobese diabetic mice. Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11548-53. doi: 10.1073/pnas.1108924108. Epub 2011 Jun 27.</citation>
    <PMID>21709219</PMID>
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    <citation>Greenbaum CJ, Beam CA, Boulware D, Gitelman SE, Gottlieb PA, Herold KC, Lachin JM, McGee P, Palmer JP, Pescovitz MD, Krause-Steinrauf H, Skyler JS, Sosenko JM; Type 1 Diabetes TrialNet Study Group. Fall in C-peptide during first 2 years from diagnosis: evidence of at least two distinct phases from composite Type 1 Diabetes TrialNet data. Diabetes. 2012 Aug;61(8):2066-73. doi: 10.2337/db11-1538. Epub 2012 Jun 11.</citation>
    <PMID>22688329</PMID>
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    <citation>Effect of intensive therapy on residual beta-cell function in patients with type 1 diabetes in the diabetes control and complications trial. A randomized, controlled trial. The Diabetes Control and Complications Trial Research Group. Ann Intern Med. 1998 Apr 1;128(7):517-23. doi: 10.7326/0003-4819-128-7-199804010-00001.</citation>
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    <citation>Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. 2010 Jun;103(12):1792-9. doi: 10.1017/S0007114509993898. Epub 2010 Feb 4.</citation>
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    <citation>Badami E, Sorini C, Coccia M, Usuelli V, Molteni L, Bolla AM, Scavini M, Mariani A, King C, Bosi E, Falcone M. Defective differentiation of regulatory FoxP3+ T cells by small-intestinal dendritic cells in patients with type 1 diabetes. Diabetes. 2011 Aug;60(8):2120-4. doi: 10.2337/db10-1201. Epub 2011 Jun 6.</citation>
    <PMID>21646390</PMID>
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    <citation>Hara N, Alkanani AK, Ir D, Robertson CE, Wagner BD, Frank DN, Zipris D. The role of the intestinal microbiota in type 1 diabetes. Clin Immunol. 2013 Feb;146(2):112-9. doi: 10.1016/j.clim.2012.12.001. Epub 2012 Dec 11.</citation>
    <PMID>23314185</PMID>
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    <citation>Ludvigsson J, Faresjo M, Hjorth M, Axelsson S, Cheramy M, Pihl M, Vaarala O, Forsander G, Ivarsson S, Johansson C, Lindh A, Nilsson NO, Aman J, Ortqvist E, Zerhouni P, Casas R. GAD treatment and insulin secretion in recent-onset type 1 diabetes. N Engl J Med. 2008 Oct 30;359(18):1909-20. doi: 10.1056/NEJMoa0804328. Epub 2008 Oct 8.</citation>
    <PMID>18843118</PMID>
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    <citation>American Diabetes Association. Standards of medical care in diabetes--2014. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80. doi: 10.2337/dc14-S014. No abstract available.</citation>
    <PMID>24357209</PMID>
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    <citation>Mejia-Leon ME, Petrosino JF, Ajami NJ, Dominguez-Bello MG, de la Barca AM. Fecal microbiota imbalance in Mexican children with type 1 diabetes. Sci Rep. 2014 Jan 22;4:3814. doi: 10.1038/srep03814.</citation>
    <PMID>24448554</PMID>
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    <citation>Patelarou E, Girvalaki C, Brokalaki H, Patelarou A, Androulaki Z, Vardavas C. Current evidence on the associations of breastfeeding, infant formula, and cow's milk introduction with type 1 diabetes mellitus: a systematic review. Nutr Rev. 2012 Sep;70(9):509-19. doi: 10.1111/j.1753-4887.2012.00513.x.</citation>
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    <citation>Murri M, Leiva I, Gomez-Zumaquero JM, Tinahones FJ, Cardona F, Soriguer F, Queipo-Ortuno MI. Gut microbiota in children with type 1 diabetes differs from that in healthy children: a case-control study. BMC Med. 2013 Feb 21;11:46. doi: 10.1186/1741-7015-11-46.</citation>
    <PMID>23433344</PMID>
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    <citation>Vaarala O. Human intestinal microbiota and type 1 diabetes. Curr Diab Rep. 2013 Oct;13(5):601-7. doi: 10.1007/s11892-013-0409-5.</citation>
    <PMID>23934614</PMID>
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    <citation>Vaarala O, Atkinson MA, Neu J. The &quot;perfect storm&quot; for type 1 diabetes: the complex interplay between intestinal microbiota, gut permeability, and mucosal immunity. Diabetes. 2008 Oct;57(10):2555-62. doi: 10.2337/db08-0331.</citation>
    <PMID>18820210</PMID>
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    <PMID>23274889</PMID>
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  <verification_date>January 2017</verification_date>
  <study_first_submitted>January 5, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 26, 2017</study_first_posted>
  <last_update_submitted>July 6, 2017</last_update_submitted>
  <last_update_submitted_qc>July 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 11, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Medical University of Warsaw</investigator_affiliation>
    <investigator_full_name>Hanna Szajewska</investigator_full_name>
    <investigator_title>Prof.</investigator_title>
  </responsible_party>
  <keyword>probiotics</keyword>
  <keyword>children</keyword>
  <keyword>remission</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 1</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03032354
org study id: AgaLidka
nct id: NCT03032354
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
They are major genera of bacteria that make up the colon flora in human, constitute
      intestinal microbial homeostasis, inhibit growth of pathogens, improve the gut mucosal
      barrier and modulate local and systemic immune responses. Changes in gut microbiota can
      influence the immune system by increasing gut permeability, intestinal inflammation, and
      impaired oral tolerance in type 1 diabetes.Taken together, the data imply that
      bacteriotherapy may potentially be used as a tool to modulate the immune system for
      preventing islet destruction. Supplementation of Lactobacillus rhamnosus GG and
      Bifidobacterium lactis BB12 improved blood glucose control in normoglycaemic pregnant women
      and reduced the frequency of gestational diabetes mellitus

      Aim of the study:

      The effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 on beta-cell
      function in children with newly diagnosed type 1 diabetes: a randomized, double blind,
      placebo-controlled trial.

      Primary end point:

      Area under the curve (AUC) of c-peptide level during during fasting and at 30,60,90,120 min
      following the start of the meal

      Intervention:

      Included patients will be randomly assigned to receive a combination of Lactobacillus
      rhamnosus GG and Bifidobacterium lactis BB12 (Probiotics Group ) or placebo (Placebo Group )
      during six months.

      The expected results:

      Beneficial effect of Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 on beta-cell
      function shown in the properly performed, methodologically accurate study would create a
      rationale for its routine use in patients with newly diagnosed type 1 diabetes.
Intervention:

      At the 6-month follow-up visit will be evaluated adherence and occurrence of side effects of
      the study procedure. The outcome measures will be assessed at the beginning of the study, and
      at the 6 and 12-month follow-up visit.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Area under the curve (AUC) during fasting and at 30,60,90,120 min following the start of the meal
time frame: 120 min responses to a mixed meal
measure: Insulin requirement (U / kg body mass )
time frame: up 60 days from diabetes recognition, at 3th, 6th, 12th month
measure: HbA1c
time frame: up to 60 days from diabetes recognition, at 3th, 6th, 12th month
measure: Weight in kilograms
time frame: up to 60 days from diabetes recognition, and at 3th, 6th, 12th month
measure: Number of participants with abnormal laboratory values and/or adverse events that are related to treatment ( eg.abdominal pain, diarrhea , constipation , vomiting,flatulence)
time frame: at 3th, 6th, 12th month
measure: Occurrence of other autoimmune diseases
time frame: at 12th month
measure: Height in meters
time frame: up to 60 days from diabetes recognition, and at 3th, 6th, 12th month
measure: BMI in kg/m2
time frame: up to 60 days from diabetes recognition, and at 3th, 6th, 12th month
measure: BMI score
time frame: up to 60 days from diabetes recognition, and at 3th, 6th, 12th month
measure: severe hypoglycemia
time frame: up to 60 days from diabetes recognition, at 3th, 6th, 12th month
measure: ketoacidosis
time frame: up to 60 days from diabetes recognition, at 3th, 6th, 12th month
measure: Fasting c- peptide concentrations in ng/ml
time frame: up to 60 days from diabetes recognition, and in: 6th, 12th month
arm group label: Probiotics arm: Probiotics group
arm group type: Experimental
description: combination of probiotics: Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12 in the same capsule
arm group label: Placebo arm: Placebo group
arm group type: Placebo Comparator
description: Placebo - maltodextrin
intervention type: Drug
intervention name: Lactobacillus rhamnosus GG and Bifidobacterium lactis BB12
description: Combination therapy of probiotics during 6 months
arm group label: Probiotics arm: Probiotics group
other name: Probiotics
intervention type: Other
intervention name: Placebo, (Placebo group)
description: Placebo during 6 months
arm group label: Placebo arm: Placebo group
other name: Maltodextrin
criteria: 
gender: All
minimum age: 8 Years
maximum age: 17 Years
healthy volunteers: No
last name: Agnieszka Szypowska, Assoc. Prof.
role: Principal Investigator
affiliation: Medical University of Warsaw
last name: Agnieszka Szypowska, Assoc. Prof.
phone: +48 509928617
email: agnieszka.szypowska@gmail.com
last name: Lidia Groele, PhD
phone: +48 608 671 083
email: lgroele@wp.pl
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PMID: 20463897
responsible party type: Principal Investigator
investigator affiliation: Medical University of Warsaw
investigator full name: Hanna Szajewska
investigator title: Prof.
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1
sharing ipd: No