Type1 DiabetesTregDiabNCT03236558
The Role of the Thymus in Type I Diabetes.
A study testing Blood collection in people with Type1 Diabetes, run by University Hospital, Toulouse at 1 site in France.
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. Read more about this study
- Who is it for?
- Ages 6 to 12 yearsHealthy volunteers can take part
- Conditions the study is for
- Type1 Diabetes
- What is being tested?
- Blood collection
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2018to Mar 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 12 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- type I diabetes patient
- having at least one age-matched sibling (healthy control)
Who cannot join
- other immunopathology
- treatment with any anti-inflammatory or immunosuppressive drugs
- puberty
- legal protection
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.
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.
Read the 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.
- Conditions
- Type1 Diabetes
- Being tested
- Blood collection
- Keywords
- Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, TCR, Repertoire
- 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.
Blood collectionProcedure or surgery
Ten cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former.
| Study group | Role | What they receive |
|---|---|---|
| Patients with diabetes | Experimental | T1D patients with blood collection Receives: Procedure: Blood collection |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Day 1
Secondary outcomes (1)
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.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2017
- Study startMar 2018 (estimated)
- Primary completionMar 2019 (estimated)
- Study completionMar 2019 (estimated)
Why it stopped: lack of Financial support
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Type1 DiabetesStudies of the same condition, open and under way.
- More trials run by University Hospital, ToulouseThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Toulouse
- Sponsor type
- University, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France
- Responsible party
- Sponsor
- Investigators
- Claire Le Tallec, MD, Principal investigator, University Hospital, Toulouse
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03236558
- Sponsor's protocol ID
- RC31/16/8254
- Acronym
- TregDiab
- Status last verified
- Mar 2020
- First submitted
- 28 Jul 2017
- Last updated
- 1 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
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.
PubMed 19359477Thiault 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.
PubMed 25939024Steffens 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.
PubMed 11027449Calder 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.
PubMed 21952680Sakaguchi 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.
PubMed 20559327Lancaster 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.
PubMed 15189396
Study at a glance
From the registry record, last updated by the sponsor on 1 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Thymic Generation of Regulatory T Lymphocytes in Type I Diabetes Patients.
- ClinicalTrials.gov ID
- NCT03236558
- Acronym / sponsor ID
- TregDiab / RC31/16/8254
- Conditions
- Type1 Diabetes
- Keywords
- Type 1 diabetes, Juvenile diabetes, Immune-tolerance, Regulatory T lymphocyte, Treg, TCR, Repertoire
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: lack of Financial support
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, ToulouseUniversity, hospital or other
- Collaborators
- Institut National de la Santé Et de la Recherche Médicale, France, Centre National de la Recherche Scientifique, France
- Study start
- Mar 2018 (estimated)
- Primary completion
- Mar 2019 (estimated)
- Study completion
- Mar 2019 (estimated)
- First posted
- 2 Aug 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with diabetes | Experimental | Procedure: Blood collectionT1D patients with blood collection |
Who may qualify
- Ages
- 6 to 12 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (2 listed)
- type I diabetes patient
- having at least one age-matched sibling (healthy control)
Key exclusion criteria (4 listed)
- other immunopathology
- treatment with any anti-inflammatory or immunosuppressive drugs
- puberty
- legal protection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood collectionTen cc of peripheral blood will be taken from patients and healthy controls as soon as possible after T1D diagnosis of the former. | Procedure or surgery | Patients with diabetes |
Primary outcome
Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls.
Time frame: Day 1
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.
1 secondary outcome
Ratio between TCR diversities expressed by Treg cells vs. conventional T cells.
Time frame: Day 1
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2020.
- Background: PubMed 19359477Ferreira 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.
- Background: PubMed 25939024Thiault 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.
- Background: PubMed 11027449Steffens 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.
- Background: PubMed 21952680Calder 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.
- Background: PubMed 20559327Sakaguchi 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.
- Background: PubMed 15189396Lancaster 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Claire Le Tallec, MD principal investigator
University Hospital, Toulouse
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Blood collection in people with Type1 Diabetes, run by University Hospital, Toulouse 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 2 inclusion and 4 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: withdrawn, as of the sponsor's last update on 1 Apr 2020. 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?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Variability of the diversity of antigen-receptors' repertoires, expressed by regulatory T cells from type I diabetes patients and healthy controls. (time frame: Day 1). 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 NCT03236558, which also lists 6 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 1 Apr 2020.