The Role of the Thymus in Type I Diabetes.

NCT ID: NCT03236558

Last Updated: 2020-04-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2018-03-31

Study Completion Date

2019-03-31

Brief Summary

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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

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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.

Conditions

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Type1 Diabetes

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Patients with diabetes

T1D patients with blood collection

Group Type EXPERIMENTAL

Blood collection

Intervention Type PROCEDURE

Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.

Interventions

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Blood collection

Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.

Intervention Type PROCEDURE

Eligibility Criteria

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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
Minimum Eligible Age

6 Years

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Institut National de la Santé Et de la Recherche Médicale, France

OTHER_GOV

Sponsor Role collaborator

Centre National de la Recherche Scientifique, France

OTHER

Sponsor Role collaborator

University Hospital, Toulouse

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claire Le Tallec, MD

Role: PRINCIPAL_INVESTIGATOR

University Hospital, Toulouse

Locations

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CHU de Toulouse

Toulouse, Midi-Pyrénées, France

Site Status

Countries

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France

References

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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.

Reference Type BACKGROUND
PMID: 19359477 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25939024 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11027449 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 21952680 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 20559327 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15189396 (View on PubMed)

Other Identifiers

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RC31/16/8254

Identifier Type: -

Identifier Source: org_study_id

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