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| ID | Type | Description | Link |
|---|---|---|---|
| 2021-A01619-32 | Other Identifier | ID RCB |
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National multi-center non-interventional case-control cohort study with collection of biological samples to characterize the autoimmune T and B lymphocytes involved in the development of type 1 diabetes.
The overall objective of this study is to define the differential characteristics of autoimmune T and B lymphocytes across individuals with T1D, other forms of diabetes or autoimmunity, and no disease. The hypothesis is that the characterization of the autoimmune T and B lymphocytes involved in T1D development may allow us to clarify the pathophysiological mechanisms of disease and to identify novel biomarkers for diagnostic, prognostic and therapeutic follow-up applications.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Type 1 diabetes | As defined by the presence of hyperglycemia and/or islet auto-antibodies. |
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| Other forms of diabetes or autoimmune endocrinopathy | Type 2 diabetes, ketosis-prone diabetes, familial diabetes, secondary diabetes, immunotherapy-induced diabetes; and/or autoimmune endocrinopathies. |
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| No diabetes | No diabetes or impaired glucose tolerance; no cancer, infectious or immune pathologies; no other condition related to autoimmune and metabolic alterations that may bias the variables under study. |
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| Lymphadenectomy planned at the occasion of an abdominal surgery | Patients undergoing a lymphadenectomy during surgery for the treatment of their underlying pathology. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Biosampling | Other | Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy. |
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| Measure | Description | Time Frame |
|---|---|---|
| To define the frequency and phenotype of autoimmune T lymphocytes reactive to islet antigens in the different study groups. | As measured by flow cytometry and sequencing techniques, with a sample size sufficient to attain a 92% statistical power and 5% alpha risk. Frequency will be expressed as number of antigen-reactive T lymphocytes per 100,000 total T lymphocytes (e.g. 20/100,000 or 0.02%). Phenotype will be expressed as percent of antigen-reactive T lymphocytes expressing a given phenotype, e.g. 20% naïve (CD45RA+CCR7+). These 2 measures will be aggregated by expressing the frequency of antigen-reactive T lymphocytes per 100,000 total T lymphocytes expressing a given phenotype, e.g. 20/100,000 antigen-reactive T lymphocytes with 20% naïve will be expressed as 4/100,000 naive antigen-reactive T lymphocytes. | 6 years |
| Measure | Description | Time Frame |
|---|---|---|
| To define the frequency and phenotype of autoimmune B lymphocytes reactive to islet antigens in the different study groups. | As measured by flow cytometry and sequencing techniques, with a sample size sufficient to attain a 92% statistical power and 5% alpha risk. Frequency will be expressed as number of antigen-reactive B lymphocytes per 100,000 total B lymphocytes (e.g. 20/100,000 or 0.02%). Phenotype will be expressed as percent of antigen-reactive B lymphocytes expressing a given phenotype, e.g. 20% memory (CD24+CD38-negative). These 2 measures will be aggregated by expressing the frequency of antigen-reactive B lymphocytes per 100,000 total B lymphocytes expressing a given phenotype, e.g. 20/100,000 antigen-reactive B lymphocytes with 20% memory will be expressed as 4/100,000 memory antigen-reactive B lymphocytes. |
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Inclusion Criteria:
Exclusion Criteria:
For all participants: ongoing pregnancy; known HIV/HCV infection; absence of social security coverage; placement under judicial protection; absence of signature of the informed study consent.
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Participants with type 1 diabetes, other forms of diabetes or autoimmune endocrinopathies and participants undergoing surgical lymphadenectomy are recruited among patients referred to participating hospital centers.
Non-diabetic participants are recruited among patient's family members and via at-large calls for healthy volunteers.
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Roberto Mallone, MD PhD | Contact | +33176535583 | roberto.mallone@inserm.fr | |
| Anna Jones | Contact | anna.jones@inserm.fr |
| Name | Affiliation | Role |
|---|---|---|
| Roberto Mallone, MD PhD | INSERM U1016 Cochin Institute | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| APHP Hôpital Avicenne | Not yet recruiting | Bobigny | Île-de-France Region | 93000 | France |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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Blood, stools, lymph nodes
| 6 years |
| To identify novel islet epitopes recognized by autoimmune T and B lymphocytes. | As measured by a lymphocyte frequency within the expected range, e.g. 1-50/million. | 6 years |
| To define the phenotype of these lymphocytes. | As defined by exploratory analyses based on omics techniques. | 6 years |
| To define the pathogenicity of these lymphocytes against pancreatic beta cells. | As measured by an in vitro killing of beta-cell targets significantly (e.g. >2-fold) higher than the killing observed with control lymphocytes. | 6 years |
| To define the antigen receptors used by these lymphocytes to recognize their target epitopes. | As defined by sequencing techniques and sequence annotation using IMGT and MiXCR. Sequence sharing and similarities across receptors will be measured using MiXCR and stringdist. | 6 years |
| To define the correlation between the biomarkers analyzed and insulin secretion. | As measured based on the correlation with fasting C-peptide levels >0.2 nM. | 6 years |
| To define the differences between lymphocytes in the blood and those in pancreatic lymph nodes. | As measured using the previous frequency and phenotype readouts. | 6 years |
| APHP Hôpital J. Verdier | Not yet recruiting | Bondy | Île-de-France Region | 93140 | France |
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| APHP Hôpital L. Mourier | Not yet recruiting | Colombes | Île-de-France Region | 92700 | France |
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| Hôpital Sud Francilien | Not yet recruiting | Corbeil-Essonnes | Île-de-France Region | 91100 | France |
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| Hôpital Mignot - Service de Pédiatrie | Not yet recruiting | Le Chesnay | Île-de-France Region | 78150 | France |
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| Hôpital Mignot - Services de Diabétologie/Endocrinologie Adultes | Not yet recruiting | Le Chesnay | Île-de-France Region | 78150 | France |
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| APHP Hôpital Kremlin-Bicêtre | Not yet recruiting | Le Kremlin-Bicêtre | Île-de-France Region | 94270 | France |
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| APHP Hôpital Lariboisière | Not yet recruiting | Paris | Île-de-France Region | 75010 | France |
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| APHP Hôpital Saint Antoine | Not yet recruiting | Paris | Île-de-France Region | 75012 | France |
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| APHP Hôpital Pitié-Salpêtrière - Service de Chirurgie | Not yet recruiting | Paris | Île-de-France Region | 75013 | France |
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| Hôpital Pitié-Salpêtrière - Service de Diabétologie | Not yet recruiting | Paris | Île-de-France Region | 75013 | France |
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| APHP Hôpital Cochin - Service de Chirurgie | Not yet recruiting | Paris | Île-de-France Region | 75014 | France |
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| APHP Hôpital Cochin - Service de Diabétologie et Immunologie Clinique | Recruiting | Paris | Île-de-France Region | 75014 | France |
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| APHP Hôpital Européen G. Pompidou | Not yet recruiting | Paris | Île-de-France Region | 75015 | France |
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| APHP Hôpital Bichat | Not yet recruiting | Paris | Île-de-France Region | 75018 | France |
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| APHP Hôpital R. Debré | Not yet recruiting | Paris | Île-de-France Region | 75019 | France |
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| Hôpital René Dubos | Not yet recruiting | Pontoise | Île-de-France Region | 95300 | France |
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| D004700 | Endocrine System Diseases |
| D007154 | Immune System Diseases |