BeAT1D: Benign Autoimmunity and Type 1 Diabetes

Institut National de la Santé Et de la Recherche Médicale, France1,160 enrolled

Overview

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.

Study Type

OBSERVATIONAL

Enrollment

1,160

Conditions

Type 1 Diabetes

Interventions

BiosamplingOTHER

Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.

Eligibility

Sex: ALLMin age: 1 YearHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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. 2. 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. 3. 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. 4. 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. 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.

Locations (17)

APHP Hôpital Avicenne

Bobigny, Île-de-France Region, France

Outcomes

Primary Outcomes

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.

Time frame: 6 years

Secondary Outcomes

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.

Time frame: 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.

Time frame: 6 years

To define the phenotype of these lymphocytes.

As defined by exploratory analyses based on omics techniques.

Central Contacts

Roberto Mallone, MD PhD

CONTACT

+33176535583 roberto.mallone@inserm.fr

Anna Jones

CONTACT

anna.jones@inserm.fr

Data from ClinicalTrials.gov

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