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Type 1 DiabetesCARegT1DNCT06427421

Characterization of Autoreactive Regulatory and Conventional CD4 T Cells in Recent Onset Type 1 Diabetes and Control Individuals

A study testing Frequency of Treg and Teffs, Phenotype of Treg and Teffs and RNA seq analysis in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 6 to 18 years
Conditions the study is for
Type 1 Diabetes
What is being tested?
Frequency of Treg and Teffs, Phenotype of Treg and Teffs and RNA seq analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
1 siteFrance
Study dates
6 May 2025to May 2027
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 6 to 18 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Newly diagnosed T1DM group:
  • Age ≥ 2 years and < 18 years on day of inclusion;
  • Weight ≥ 12 kg;
  • Newly diagnosed T1DM, diagnosis defined according to International Society of Pediatric and Adolescent Diabetes (ISPAD) criteria by: hyperglycemia > 2g/L and/or ketonemia and/or polyuro-polydipsia and/or weight loss ;
  • Absence of other associated inflammatory or autoimmune diseases;
  • Affiliation with a health insurance scheme or beneficiary (excluding AME);
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  • Written consent of parental guardians;
  • Ability to understand and read French.
  • Control group :
  • Age ≥ 2 years and < 18 years on the day of inclusion;
  • Weight ≥ 12 kg;
  • No personal history of T1DM;
  • Affiliation with a health insurance scheme or entitled person (excluding AME);
  • Written consent from parental guardians;
  • Ability to understand and read French.

Who cannot join

  • Newly diagnosed T1DM group:
  • Use of oral or intravenous corticosteriods in the month prior to blood sampling
  • Contraindication to the use of anaesthetic cream for blood sampling.
  • Control group :
  • History of autoimmune or inflammatory disease
  • Use of oral or intravenous corticosteriods in the month prior to blood sampling
  • Contraindication to the use of anaesthetic cream for blood sampling

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Jacques BELTRAND, MD, PhD contact

+33 1 40 61 53 20

jacques.beltrand@aphp.fr

Sarah BOUCHARD contact

+ 33 1 42 19 28 79

sarah.bouchard@aphp.fr

France1 site, 1 recruiting

  • Hôpital Necker Enfants Malades

    Paris, 75015

    Jacques BELTRAND, MD, PhD, +33 1 40 61 53 20, jacques.beltrand@aphp.fr

    Sarah BOUCHARD, + 33 1 42 19 28 79, sarah.bouchard@aphp.fr

    Recruiting

Other trials in France

About this study

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

Read the 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 major/important 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.

Conditions
Type 1 Diabetes
Being tested
Frequency of Treg and Teffs, Phenotype of Treg and Teffs, RNA seq analysis, HLA typing, beta-cell autoantibody dosage
Keywords
Type 1 Diabetes, Regulatory T cells, Pathophysiology of T1DM
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Frequency of Treg and TeffsBiological

    additionnal blood sampling at inclusion

  • Phenotype of Treg and TeffsBiological

    additionnal blood sampling at inclusion

  • RNA seq analysisBiological

    additionnal blood sampling at inclusion

  • HLA typingBiological

    additionnal blood sampling at inclusion

  • beta-cell autoantibody dosageBiological

    additionnal blood sampling at inclusion

  • Glycated haemoglobin (HbA1C) dosageBiological

    additionnal blood sampling at inclusion

  • blood glucose dosageBiological

    additionnal blood sampling at inclusion

  • C-peptide dosageBiological

    additionnal blood sampling at inclusion

Study groups in NCT06427421
Study groupRoleWhat they receive
Newly diagnosed T1DM groupOtherchildren aged 2 to under 18 on the day of inclusion, with a recent diagnosis of type 1 diabetes
Receives: Biological: Frequency of Treg and Teffs; Biological: Phenotype of Treg and Teffs; Biological: RNA seq analysis; Biological: HLA typing; Biological: beta-cell autoantibody dosage
Control groupOtherchildren aged 2 to under 18 on the day of inclusion, with no history of type 1 diabetes
Receives: Biological: Frequency of Treg and Teffs; Biological: Phenotype of Treg and Teffs; Biological: RNA seq analysis; Biological: HLA typing; Biological: beta-cell autoantibody dosage; Biological: Glycated haemoglobin (HbA1C) dosage; Biological: blood glucose dosage; Biological: C-peptide dosage

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Frequency and phenotype of Tregs

    study the frequency and phenotype of insulin-specific autoreactive Tregs lymphocytes among CD4+ T lymphocytes in children with T1DM and compare these values with those of controls. These parameters will be analyzed by flow cytometry using immune cells from blood samples taken from the T1DM and control groups.

    Measured: Within 4 weeks of T1DM diagnosis

Secondary outcomes (5)

  1. HLA testing

    Description : the HLA of T1DM and controls will be analyzed by qPCR. This will make it possible to associate the results obtained during the analysis of the main criteria with the HLA of each individual.

    Measured: Within 4 weeks of T1DM diagnosis

  2. Isolate insulin-specific Tregs and Teffs cells

    Insulin-specific Tregs and Teffs cells will be isolated by flow cytometry

    Measured: Within 4 weeks of T1DM diagnosis

  3. Treg and Teffs transcriptome

    their transcriptome and TCR will be determined by single-cell transcriptomics analysis (scRNAseq).

    Measured: Within 4 weeks of T1DM diagnosis

  4. Full TCR repertoire of Tregs and Teffs

    Following flow cytometry, the different repertoires will be compared between the DT1 and control groups.

    Measured: Within 4 weeks of T1DM diagnosis

  5. Machine learning analysis

    Machine learning analysis of the data obtained (TCR, transcriptome, frequency and phenotype of insulin-specific Tregs and Teffs) to predict the relationship between TCR and functional properties of Tregs and Teffs in patients and controls

    Measured: Within 4 weeks of T1DM diagnosis

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 May 2024
  2. Study start6 May 2025
  3. Primary completionMay 2027 (estimated)
  4. Study completionMay 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06427421
Sponsor's protocol ID
APHP230664
Other IDs
2024-A00696-41
Acronym
CARegT1D
Status last verified
Oct 2025
First submitted
16 May 2024
Last updated
20 Nov 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Patterson CC, Harjutsalo V, Rosenbauer J, Neu A, Cinek O, Skrivarhaug T, Rami-Merhar B, Soltesz G, Svensson J, Parslow RC, Castell C, Schoenle EJ, Bingley PJ, Dahlquist G, Jarosz-Chobot PK, Marciulionyte D, Roche EF, Rothe U, Bratina N, Ionescu-Tirgoviste C, Weets I, Kocova M, Cherubini V, Rojnic Putarek N, deBeaufort CE, Samardzic M, Green A. Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study. Diabetologia. 2019 Mar;62(3):408-417. doi: 10.1007/s00125-018-4763-3. Epub 2018 Nov 28.

    PubMed 30483858

  • Mobasseri M, Shirmohammadi M, Amiri T, Vahed N, Hosseini Fard H, Ghojazadeh M. Prevalence and incidence of type 1 diabetes in the world: a systematic review and meta-analysis. Health Promot Perspect. 2020 Mar 30;10(2):98-115. doi: 10.34172/hpp.2020.18. eCollection 2020.

    PubMed 32296622

  • Foster NC, Beck RW, Miller KM, Clements MA, Rickels MR, DiMeglio LA, Maahs DM, Tamborlane WV, Bergenstal R, Smith E, Olson BA, Garg SK. State of Type 1 Diabetes Management and Outcomes from the T1D Exchange in 2016-2018. Diabetes Technol Ther. 2019 Feb;21(2):66-72. doi: 10.1089/dia.2018.0384. Epub 2019 Jan 18.

    PubMed 30657336

  • Miller KM, Foster NC, Beck RW, Bergenstal RM, DuBose SN, DiMeglio LA, Maahs DM, Tamborlane WV; T1D Exchange Clinic Network. Current state of type 1 diabetes treatment in the U.S.: updated data from the T1D Exchange clinic registry. Diabetes Care. 2015 Jun;38(6):971-8. doi: 10.2337/dc15-0078.

    PubMed 25998289

  • Bougneres PF, Carel JC, Castano L, Boitard C, Gardin JP, Landais P, Hors J, Mihatsch MJ, Paillard M, Chaussain JL, et al. Factors associated with early remission of type I diabetes in children treated with cyclosporine. N Engl J Med. 1988 Mar 17;318(11):663-70. doi: 10.1056/NEJM198803173181103.

    PubMed 3125434

  • Parving HH, Tarnow L, Nielsen FS, Rossing P, Mandrup-Poulsen T, Osterby R, Nerup J. Cyclosporine nephrotoxicity in type 1 diabetic patients. A 7-year follow-up study. Diabetes Care. 1999 Mar;22(3):478-83. doi: 10.2337/diacare.22.3.478.

    PubMed 10097932

  • Herold KC, Bundy BN, Long SA, Bluestone JA, DiMeglio LA, Dufort MJ, Gitelman SE, Gottlieb PA, Krischer JP, Linsley PS, Marks JB, Moore W, Moran A, Rodriguez H, Russell WE, Schatz D, Skyler JS, Tsalikian E, Wherrett DK, Ziegler AG, Greenbaum CJ; Type 1 Diabetes TrialNet Study Group. An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes. N Engl J Med. 2019 Aug 15;381(7):603-613. doi: 10.1056/NEJMoa1902226. Epub 2019 Jun 9.

    PubMed 31180194

  • Keymeulen B, Vandemeulebroucke E, Ziegler AG, Mathieu C, Kaufman L, Hale G, Gorus F, Goldman M, Walter M, Candon S, Schandene L, Crenier L, De Block C, Seigneurin JM, De Pauw P, Pierard D, Weets I, Rebello P, Bird P, Berrie E, Frewin M, Waldmann H, Bach JF, Pipeleers D, Chatenoud L. Insulin needs after CD3-antibody therapy in new-onset type 1 diabetes. N Engl J Med. 2005 Jun 23;352(25):2598-608. doi: 10.1056/NEJMoa043980.

    PubMed 15972866

  • Vignali DA, Collison LW, Workman CJ. How regulatory T cells work. Nat Rev Immunol. 2008 Jul;8(7):523-32. doi: 10.1038/nri2343.

    PubMed 18566595

  • Corthay A. How do regulatory T cells work? Scand J Immunol. 2009 Oct;70(4):326-36. doi: 10.1111/j.1365-3083.2009.02308.x.

    PubMed 19751267

  • Visperas A, Vignali DA. Are Regulatory T Cells Defective in Type 1 Diabetes and Can We Fix Them? J Immunol. 2016 Nov 15;197(10):3762-3770. doi: 10.4049/jimmunol.1601118.

    PubMed 27815439

  • Bluestone JA, Buckner JH, Fitch M, Gitelman SE, Gupta S, Hellerstein MK, Herold KC, Lares A, Lee MR, Li K, Liu W, Long SA, Masiello LM, Nguyen V, Putnam AL, Rieck M, Sayre PH, Tang Q. Type 1 diabetes immunotherapy using polyclonal regulatory T cells. Sci Transl Med. 2015 Nov 25;7(315):315ra189. doi: 10.1126/scitranslmed.aad4134.

    PubMed 26606968

  • Marek-Trzonkowska N, Mysliwiec M, Dobyszuk A, Grabowska M, Techmanska I, Juscinska J, Wujtewicz MA, Witkowski P, Mlynarski W, Balcerska A, Mysliwska J, Trzonkowski P. Administration of CD4+CD25highCD127- regulatory T cells preserves beta-cell function in type 1 diabetes in children. Diabetes Care. 2012 Sep;35(9):1817-20. doi: 10.2337/dc12-0038. Epub 2012 Jun 20.

    PubMed 22723342

  • Dong S, Hiam-Galvez KJ, Mowery CT, Herold KC, Gitelman SE, Esensten JH, Liu W, Lares AP, Leinbach AS, Lee M, Nguyen V, Tamaki SJ, Tamaki W, Tamaki CM, Mehdizadeh M, Putnam AL, Spitzer MH, Ye CJ, Tang Q, Bluestone JA. The effect of low-dose IL-2 and Treg adoptive cell therapy in patients with type 1 diabetes. JCI Insight. 2021 Sep 22;6(18):e147474. doi: 10.1172/jci.insight.147474.

    PubMed 34324441

  • Kieback E, Hilgenberg E, Stervbo U, Lampropoulou V, Shen P, Bunse M, Jaimes Y, Boudinot P, Radbruch A, Klemm U, Kuhl AA, Liblau R, Hoevelmeyer N, Anderton SM, Uckert W, Fillatreau S. Thymus-Derived Regulatory T Cells Are Positively Selected on Natural Self-Antigen through Cognate Interactions of High Functional Avidity. Immunity. 2016 May 17;44(5):1114-26. doi: 10.1016/j.immuni.2016.04.018.

    PubMed 27192577

Questions about this trial

What is this clinical trial studying?

A study testing Frequency of Treg and Teffs, Phenotype of Treg and Teffs and RNA seq analysis in people with Type 1 Diabetes, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Jacques BELTRAND, MD, PhD (+33 1 40 61 53 20, jacques.beltrand@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Frequency and phenotype of Tregs (time frame: Within 4 weeks of T1DM diagnosis). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06427421, which also lists 18 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.

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