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The Role of the Thymus in Type I Diabetes. (TregDiab)

Primary Purpose

Type1 Diabetes

Status
Withdrawn
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Blood collection
Sponsored by
University Hospital, Toulouse
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Type1 Diabetes focused on measuring Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, TCR, Repertoire

Eligibility Criteria

6 Years - 12 Years (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • type I diabetes patient
  • having at least one age-matched sibling (healthy control)

Exclusion Criteria:

  • other immunopathology
  • treatment with any anti-inflammatory or immunosuppressive drugs
  • puberty
  • legal protection

Sites / Locations

  • CHU de Toulouse

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with diabetes

Arm Description

T1D patients with blood collection

Outcomes

Primary Outcome Measures

Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.
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.

Secondary Outcome Measures

Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.
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.

Full Information

First Posted
July 28, 2017
Last Updated
March 30, 2020
Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France
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1. Study Identification

Unique Protocol Identification Number
NCT03236558
Brief Title
The Role of the Thymus in Type I Diabetes.
Acronym
TregDiab
Official Title
Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Withdrawn
Why Stopped
lack of Financial support
Study Start Date
March 2018 (Anticipated)
Primary Completion Date
March 2019 (Anticipated)
Study Completion Date
March 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Toulouse
Collaborators
Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Type1 Diabetes
Keywords
Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, TCR, Repertoire

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Patients with diabetes
Arm Type
Experimental
Arm Description
T1D patients with blood collection
Intervention Type
Procedure
Intervention Name(s)
Blood collection
Intervention Description
Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.
Primary Outcome Measure Information:
Title
Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.
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.
Time Frame
Day 1
Secondary Outcome Measure Information:
Title
Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.
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.
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: type I diabetes patient having at least one age-matched sibling (healthy control) Exclusion Criteria: other immunopathology treatment with any anti-inflammatory or immunosuppressive drugs puberty legal protection
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claire Le Tallec, MD
Organizational Affiliation
CHU Toulouse
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU de Toulouse
City
Toulouse
State/Province
Midi-Pyrénées
ZIP/Postal Code
31059
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
19359477
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.
Results Reference
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PubMed Identifier
25939024
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.
Results Reference
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PubMed Identifier
11027449
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.
Results Reference
background
PubMed Identifier
21952680
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.
Results Reference
background
PubMed Identifier
20559327
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.
Results Reference
background
PubMed Identifier
15189396
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.
Results Reference
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The Role of the Thymus in Type I Diabetes.

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