Ignite Creation Date:
2024-06-16 @ 11:47 AM
Last Modification Date:
2024-10-26 @ 3:30 PM
Study NCT ID:
NCT06427421
Status:
NOT_YET_RECRUITING
Last Update Posted:
2024-05-23
First Post:
2024-05-16
Brief Title:
Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals
Sponsor:
Assistance Publique - Hôpitaux de Paris
Organization:
Assistance Publique - Hôpitaux de Paris
Study Overview
Official Title:
Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals
Status:
NOT_YET_RECRUITING
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CARegT1D
Brief Summary:
Type 1 diabetes T1D is caused by an autoimmune response leading to the destruction of pancreatic beta cells The disease association with particular HLA class II alleles particularly HLA-DQ8 indicates the implication of CD4 T cells in its aetiology The hypothesis is therefore that T1D starts by the loss of tolerance in autoreactive CD4 T cells This might result from alterations in conventional autoreactive CD4 T cells Tcons which drive disease or autoreactive regulatory CD4 T cells expressing the transcription factor FOXP3 Tregs which normally maintain immune tolerance The investigators expect that the characterization of HLA-DQ8-restricted Tcons and Tregs in recent onset HLA-DQ8 T1D patients shall shed light on the molecular mechanisms underpinning T1D development This knowledge will guide the development of novel cell therapies harnessing the power of genetically engineered Tregs expressing the relevant antigen receptor to restore immune homeostasis upon cell transfer The ultimate goal is to reach a curative effect
Detailed Description:
During the development of type 1 diabetes T1DM regulatory T cells Treg are modified and their protective role is no longer optimal particularly against pathology-specific autoreactive antigens The hypothesis is that in patients with T1DM the function and phenotype of Treg cells as well as their receptor repertoire for the antigen to which they are specific TCR no longer allow them to control tolerance The in-depth study of these cells at both genetic and molecular levels will enable a major breakthrough in our understanding of the pathophysiology of T1DM and in the development of targeted cell therapy
The investigators expect majorimportant differences between patient Tregs and those of the control population in this study at the molecular phenotypic and functional levels These differences will highlight the TCRs recognizing the target self-antigens In this way investigators expect to be able to select a limited number of Treg TCRs that could ultimately be used in cell therapy to restore the protective role of Tregs in these patients
Thus this knowledge will enable to propose in the future a more effective immunotherapy with a long-term effect in order to improve the management of patients with autoimmune diabetes and potentially cure them
Accordingly yhe investigators will study insulin-specific Tregs in T1DM patients and control individuals as well as conventional T cells directed against the same antigen which in patients are implicated in the disease This will include a study of their functional status their transcriptomic profile as well as their TCRs and their fine recognition properties of the major diabetes self-antigen insulin
The investigators expect majorimportant differences between patient Tregs and those of the control population in this study at the molecular phenotypic and functional levels These differences will highlight the TCRs recognizing the target self-antigens In this way investigators expect to be able to select a limited number of Treg TCRs that could ultimately be used in cell therapy to restore the protective role of Tregs in these patients
Thus this knowledge will enable to propose in the future a more effective immunotherapy with a long-term effect in order to improve the management of patients with autoimmune diabetes and potentially cure them
Accordingly yhe investigators will study insulin-specific Tregs in T1DM patients and control individuals as well as conventional T cells directed against the same antigen which in patients are implicated in the disease This will include a study of their functional status their transcriptomic profile as well as their TCRs and their fine recognition properties of the major diabetes self-antigen insulin
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 2024-A00696-41 | OTHER | ID-RCB | None |