BeAT1D: Benign Autoimmunity and Type 1 Diabetes

Sponsor

Institut National de la Santé Et de la Recherche Médicale, France (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05139784

Collaborator

(none)

740

Enrollment

Locations

Anticipated Duration (Months)

43.5

Patients Per Site

0.7

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Other: Biosampling

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

740 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

BeAT1D: Benign Autoimmunity and Type 1 Diabetes

Anticipated Study Start Date :

Sep 1, 2022

Anticipated Primary Completion Date :

Dec 1, 2027

Anticipated Study Completion Date :

Dec 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Type 1 diabetes As defined by the presence of hyperglycemia and/or islet auto-antibodies.	Other: Biosampling Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
Other forms of diabetes or autoimmune endocrinopathy Type 2 diabetes, ketosis-prone diabetes, familial diabetes, secondary diabetes, immunotherapy-induced diabetes; and/or autoimmune endocrinopathies.	Other: Biosampling Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
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.	Other: Biosampling Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.
Lymphadenectomy planned at the occasion of an abdominal surgery Patients undergoing a lymphadenectomy during surgery for the treatment of their underlying pathology.	Other: Biosampling Collection of blood and stool specimens; and collection of lymph node specimens for the group undergoing surgical lymphadenectomy.

Outcome Measures

Primary Outcome Measures

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

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 phenotype of these lymphocytes. [6 years]
As defined by exploratory analyses based on omics techniques.
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 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 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 differences between lymphocytes in the blood and those in pancreatic lymph nodes. [6 years]
As measured using the previous frequency and phenotype readouts.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Year and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

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.

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	APHP Hôpital Avicenne	Bobigny	Ile-de-France	France	93000
2	APHP Hôpital J. Verdier	Bondy	Ile-de-France	France	93140
3	APHP Hôpital L. Mourier	Colombes	Ile-de-France	France	92700
4	Hôpital Sud Francilien	Corbeil-Essonnes	Ile-de-France	France	91100
5	Hôpital Mignot - Service de Pédiatrie	Le Chesnay	Ile-de-France	France	78150
6	Hôpital Mignot - Services de Diabétologie/Endocrinologie Adultes	Le Chesnay	Ile-de-France	France	78150
7	APHP Hôpital Kremlin-Bicêtre	Le Kremlin-Bicêtre	Ile-de-France	France	94270
8	APHP Hôpital Lariboisière	Paris	Ile-de-France	France	75010
9	APHP Hôpital Saint Antoine	Paris	Ile-de-France	France	75012
10	APHP Hôpital Pitié-Salpêtrière - Service de Chirurgie	Paris	Ile-de-France	France	75013
11	Hôpital Pitié-Salpêtrière - Service de Diabétologie	Paris	Ile-de-France	France	75013
12	APHP Hôpital Cochin - Service de Chirurgie	Paris	Ile-de-France	France	75014
13	APHP Hôpital Cochin - Service de Diabétologie et Immunologie Clinique	Paris	Ile-de-France	France	75014
14	APHP Hôpital Européen G. Pompidou	Paris	Ile-de-France	France	75015
15	APHP Hôpital Bichat	Paris	Ile-de-France	France	75018
16	APHP Hôpital R. Debré	Paris	Ile-de-France	France	75019
17	Hôpital René Dubos	Pontoise	Ile-de-France	France	95300