BeAT1D: Benign Autoimmunity and Type 1 Diabetes
- Conditions
- Type 1 Diabetes
- Interventions
- Other: Biosampling
- Registration Number
- NCT05139784
- Lead Sponsor
- Institut National de la Santé Et de la Recherche Médicale, France
- Brief Summary
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.
- Detailed Description
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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 740
- Type 1 diabetes: type 1 diabetes, as defined by hyperglycemia and long-term insulin therapy started within 6 months from clinical onset; and/or the presence of at least one anti-islet auto-antibody.
- Other forms of diabetes or autoimmune endocrinopathy: other forms of diabetes (e.g. type 2, ketosis-prone, familial, secondary, immunotherapy-induced diabetes); and/or other autoimmune endocrinopathies, isolated or multiple.
- No diabetes: absence of diabetes or impaired glucose tolerance; absence of tumor, infectious or immune pathologies, or other conditions related to autoimmune or metabolic alterations that may bias the variables under study.
- Lymphadenectomy planned in the frame of an abdominal surgery: pancreatic lymphadenectomy planned at the occasion of an abdominal surgery for the treatment of an underlying condition.
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.
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description Type 1 diabetes Biosampling As defined by the presence of hyperglycemia and/or islet auto-antibodies. Other forms of diabetes or autoimmune endocrinopathy Biosampling Type 2 diabetes, ketosis-prone diabetes, familial diabetes, secondary diabetes, immunotherapy-induced diabetes; and/or autoimmune endocrinopathies. No diabetes Biosampling 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. Lymphadenectomy planned at the occasion of an abdominal surgery Biosampling Patients undergoing a lymphadenectomy during surgery for the treatment of their underlying pathology.
- Primary Outcome Measures
Name Time Method To define the frequency and phenotype of autoimmune T lymphocytes reactive to islet antigens in the different study groups. 6 years 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.
- Secondary Outcome Measures
Name Time Method To define the frequency and phenotype of autoimmune B lymphocytes reactive to islet antigens in the different study groups. 6 years 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.To identify novel islet epitopes recognized by autoimmune T and B lymphocytes. 6 years As measured by a lymphocyte frequency within the expected range, e.g. 1-50/million.
To define the correlation between the biomarkers analyzed and insulin secretion. 6 years As measured based on the correlation with fasting C-peptide levels \>0.2 nM.
To define the antigen receptors used by these lymphocytes to recognize their target epitopes. 6 years 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.
To define the differences between lymphocytes in the blood and those in pancreatic lymph nodes. 6 years As measured using the previous frequency and phenotype readouts.
To define the pathogenicity of these lymphocytes against pancreatic beta cells. 6 years As measured by an in vitro killing of beta-cell targets significantly (e.g. \>2-fold) higher than the killing observed with control lymphocytes.
To define the phenotype of these lymphocytes. 6 years As defined by exploratory analyses based on omics techniques.
Trial Locations
- Locations (17)
APHP Hôpital J. Verdier
🇫🇷Bondy, Ile-de-France, France
APHP Hôpital Cochin - Service de Diabétologie et Immunologie Clinique
🇫🇷Paris, Ile-de-France, France
Hôpital René Dubos
🇫🇷Pontoise, Ile-de-France, France
APHP Hôpital Avicenne
🇫🇷Bobigny, Ile-de-France, France
APHP Hôpital L. Mourier
🇫🇷Colombes, Ile-de-France, France
Hôpital Sud Francilien
🇫🇷Corbeil-Essonnes, Ile-de-France, France
APHP Hôpital Kremlin-Bicêtre
🇫🇷Le Kremlin-Bicêtre, Ile-de-France, France
APHP Hôpital Pitié-Salpêtrière - Service de Chirurgie
🇫🇷Paris, Ile-de-France, France
Hôpital Pitié-Salpêtrière - Service de Diabétologie
🇫🇷Paris, Ile-de-France, France
Hôpital Mignot - Services de Diabétologie/Endocrinologie Adultes
🇫🇷Le Chesnay, Ile-de-France, France
APHP Hôpital Lariboisière
🇫🇷Paris, Ile-de-France, France
APHP Hôpital Cochin - Service de Chirurgie
🇫🇷Paris, Ile-de-France, France
APHP Hôpital Saint Antoine
🇫🇷Paris, Ile-de-France, France
APHP Hôpital Européen G. Pompidou
🇫🇷Paris, Ile-de-France, France
Hôpital Mignot - Service de Pédiatrie
🇫🇷Le Chesnay, Ile-de-France, France
APHP Hôpital Bichat
🇫🇷Paris, Ile-de-France, France
APHP Hôpital R. Debré
🇫🇷Paris, Ile-de-France, France