The Role of the Thymus in Type I Diabetes.

Type1 Diabetes Clinical Trial

— TregDiab  

Official title:

Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT03236558
• Other study ID #: RC31/16/8254
• Status: Withdrawn
• Phase: N/A
• Start date: March 2018
• Est. completion date: March 2019

Study information

• Verified date: March 2020
• Source: University Hospital, Toulouse
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type1 Diabetes

Intervention

Procedure:
• 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.

Locations

Country	Name	City	State
France	CHU de Toulouse	Toulouse	Midi-Pyrénées

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Toulouse	Centre National de la Recherche Scientifique, France, Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

References & Publications (6)

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. Review. — View 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. — View 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. — View 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. Review. — View 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 naïve phenotypes. Clin Immunol. 2000 Nov;97(2):95-101. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Day 1
Secondary	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.	Day 1