<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/NCT03236558</url>
  </required_header>
  <id_info>
    <org_study_id>RC31/16/8254</org_study_id>
    <nct_id>NCT03236558</nct_id>
  </id_info>
  <brief_title>The Role of the Thymus in Type I Diabetes.</brief_title>
  <acronym>TregDiab</acronym>
  <official_title>Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Hospital, Toulouse</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Institut National de la Santé Et de la Recherche Médicale, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Centre National de la Recherche Scientifique, France</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Hospital, Toulouse</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>
      Regulatory T lymphocytes play a major role in the protection from autoimmune pathology.&#xD;
      Defects in immunosuppression mediated by these cells is therefore suspected to contribute to&#xD;
      these diseases. This issue has very little been studied in humans.Regulatory T cells&#xD;
      emigrated from the thymus will be isolated from the blood of patients and healthy controls.&#xD;
      The repertoire of antigen-receptors will be analysed by high throughput sequencing and its&#xD;
      diversity estimated using appropriate statistical models borrowed from ecology.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In the thymus of an animal model of type I diabetes, the population of regulatory T cells&#xD;
      expresses a repertoire of antigen receptors that is approximately ten-fold less diverse than&#xD;
      that found in mice resistant to autoimmune pathology. Genetic models later showed that this&#xD;
      reduced diversity was involved in the susceptibility to diabetes. Researchers study the&#xD;
      diversity of the TCR expressed by regulatory T cells from paediatric type I diabetes patients&#xD;
      and controls. Regulatory T cells emigrated from the thymus will be isolated from the blood of&#xD;
      patients and healthy controls. The repertoire of antigen-receptors will be analysed by high&#xD;
      throughput sequencing and its diversity estimated using appropriate statistical models&#xD;
      borrowed from ecology.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    lack of Financial support&#xD;
  </why_stopped>
  <start_date type="Anticipated">March 2018</start_date>
  <completion_date type="Anticipated">March 2019</completion_date>
  <primary_completion_date type="Anticipated">March 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.</measure>
    <time_frame>Day 1</time_frame>
    <description>Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the messenger ribonucleic acid (mRNA) of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.</measure>
    <time_frame>Day 1</time_frame>
    <description>Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the mRNA of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Type1 Diabetes</condition>
  <arm_group>
    <arm_group_label>Patients with diabetes</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>T1D patients with blood collection</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Blood collection</intervention_name>
    <description>Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.</description>
    <arm_group_label>Patients with diabetes</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  type I diabetes patient&#xD;
&#xD;
          -  having at least one age-matched sibling (healthy control)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  other immunopathology&#xD;
&#xD;
          -  treatment with any anti-inflammatory or immunosuppressive drugs&#xD;
&#xD;
          -  puberty&#xD;
&#xD;
          -  legal protection&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>6 Years</minimum_age>
    <maximum_age>12 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Claire Le Tallec, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>CHU Toulouse</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>CHU de Toulouse</name>
      <address>
        <city>Toulouse</city>
        <state>Midi-Pyrénées</state>
        <zip>31059</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <reference>
    <citation>Ferreira C, Singh Y, Furmanski AL, Wong FS, Garden OA, Dyson J. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8320-5. doi: 10.1073/pnas.0808493106. Epub 2009 Apr 9.</citation>
    <PMID>19359477</PMID>
  </reference>
  <reference>
    <citation>Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34. doi: 10.1038/ni.3150. Epub 2015 May 4.</citation>
    <PMID>25939024</PMID>
  </reference>
  <reference>
    <citation>Steffens CM, Al-Harthi L, Shott S, Yogev R, Landay A. Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naive phenotypes. Clin Immunol. 2000 Nov;97(2):95-101. doi: 10.1006/clim.2000.4938.</citation>
    <PMID>11027449</PMID>
  </reference>
  <reference>
    <citation>Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL. Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation. 2011;18(5):281-9. doi: 10.1159/000329496. Epub 2011 Sep 22.</citation>
    <PMID>21952680</PMID>
  </reference>
  <reference>
    <citation>Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010 Jul;10(7):490-500. doi: 10.1038/nri2785. Epub 2010 Jun 18.</citation>
    <PMID>20559327</PMID>
  </reference>
  <reference>
    <citation>Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12. doi: 10.1111/j..2002.384.doc.x.</citation>
    <PMID>15189396</PMID>
  </reference>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>March 30, 2020</last_update_submitted>
  <last_update_submitted_qc>March 30, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">April 1, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Type 1 diabetes</keyword>
  <keyword>Juvenile diabetes</keyword>
  <keyword>Immune-tolerance</keyword>
  <keyword>Regulatory T lymphocyte</keyword>
  <keyword>Treg</keyword>
  <keyword>TCR</keyword>
  <keyword>Repertoire</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>
  <!-- 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/NCT03236558
org study id: RC31/16/8254
nct id: NCT03236558
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Regulatory T lymphocytes play a major role in the protection from autoimmune pathology.
      Defects in immunosuppression mediated by these cells is therefore suspected to contribute to
      these diseases. This issue has very little been studied in humans.Regulatory T cells
      emigrated from the thymus will be isolated from the blood of patients and healthy controls.
      The repertoire of antigen-receptors will be analysed by high throughput sequencing and its
      diversity estimated using appropriate statistical models borrowed from ecology.
In the thymus of an animal model of type I diabetes, the population of regulatory T cells
      expresses a repertoire of antigen receptors that is approximately ten-fold less diverse than
      that found in mice resistant to autoimmune pathology. Genetic models later showed that this
      reduced diversity was involved in the susceptibility to diabetes. Researchers study the
      diversity of the TCR expressed by regulatory T cells from paediatric type I diabetes patients
      and controls. Regulatory T cells emigrated from the thymus will be isolated from the blood of
      patients and healthy controls. The repertoire of antigen-receptors will be analysed by high
      throughput sequencing and its diversity estimated using appropriate statistical models
      borrowed from ecology.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.
time frame: Day 1
description: Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the messenger ribonucleic acid (mRNA) of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing.
measure: Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.
time frame: Day 1
description: Treg from the pediatric patients and the control subjects' blood will be isolated by cytometry, the mRNA of these cells will be isolated, and the analysis of the alpha and beta chains of the TCRs will be carried out by high-throughput sequencing.
arm group label: Patients with diabetes
arm group type: Experimental
description: T1D patients with blood collection
intervention type: Procedure
intervention name: Blood collection
description: Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.
arm group label: Patients with diabetes
criteria: 
gender: All
minimum age: 6 Years
maximum age: 12 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Claire Le Tallec, MD
role: Principal Investigator
affiliation: CHU Toulouse
facility: 
country: France
citation: Ferreira C, Singh Y, Furmanski AL, Wong FS, Garden OA, Dyson J. Non-obese diabetic mice select a low-diversity repertoire of natural regulatory T cells. Proc Natl Acad Sci U S A. 2009 May 19;106(20):8320-5. doi: 10.1073/pnas.0808493106. Epub 2009 Apr 9.
PMID: 19359477
citation: Thiault N, Darrigues J, Adoue V, Gros M, Binet B, Perals C, Leobon B, Fazilleau N, Joffre OP, Robey EA, van Meerwijk JP, Romagnoli P. Peripheral regulatory T lymphocytes recirculating to the thymus suppress the development of their precursors. Nat Immunol. 2015 Jun;16(6):628-34. doi: 10.1038/ni.3150. Epub 2015 May 4.
PMID: 25939024
citation: Steffens CM, Al-Harthi L, Shott S, Yogev R, Landay A. Evaluation of thymopoiesis using T cell receptor excision circles (TRECs): differential correlation between adult and pediatric TRECs and naive phenotypes. Clin Immunol. 2000 Nov;97(2):95-101. doi: 10.1006/clim.2000.4938.
PMID: 11027449
citation: Calder AE, Hince MN, Dudakov JA, Chidgey AP, Boyd RL. Thymic involution: where endocrinology meets immunology. Neuroimmunomodulation. 2011;18(5):281-9. doi: 10.1159/000329496. Epub 2011 Sep 22.
PMID: 21952680
citation: Sakaguchi S, Miyara M, Costantino CM, Hafler DA. FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol. 2010 Jul;10(7):490-500. doi: 10.1038/nri2785. Epub 2010 Jun 18.
PMID: 20559327
citation: Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. J Eval Clin Pract. 2004 May;10(2):307-12. doi: 10.1111/j..2002.384.doc.x.
PMID: 15189396
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 1