BeAT1D: Benign Autoimmunity and Type 1 Diabetes

Type 1 Diabetes Clinical Trial

— BeAT1D  

Official title:

BeAT1D: Benign Autoimmunity and Type 1 Diabetes

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05139784
• Other study ID #: C20-61
• Secondary ID: 2021-A01619-32
• Status: Recruiting
• Start date: October 24, 2022
• Est. completion date: December 2027

Study information

• Verified date: March 2024
• Source: Institut National de la Santé Et de la Recherche Médicale, France
• Contact: Roberto Mallone, MD PhD
• Phone: +33176535583
• Email: roberto.mallone[@]inserm.fr
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 740
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Year and older

Eligibility

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.

Related Conditions & MeSH terms

• Autoimmune Diseases
• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes

Intervention

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

Locations

Country	Name	City	State
France	APHP Hôpital Avicenne	Bobigny	Ile-de-France
France	APHP Hôpital J. Verdier	Bondy	Ile-de-France
France	APHP Hôpital L. Mourier	Colombes	Ile-de-France
France	Hôpital Sud Francilien	Corbeil-Essonnes	Ile-de-France
France	Hôpital Mignot - Service de Pédiatrie	Le Chesnay	Ile-de-France
France	Hôpital Mignot - Services de Diabétologie/Endocrinologie Adultes	Le Chesnay	Ile-de-France
France	APHP Hôpital Kremlin-Bicêtre	Le Kremlin-Bicêtre	Ile-de-France
France	APHP Hôpital Bichat	Paris	Ile-de-France
France	APHP Hôpital Cochin - Service de Chirurgie	Paris	Ile-de-France
France	APHP Hôpital Cochin - Service de Diabétologie et Immunologie Clinique	Paris	Ile-de-France
France	APHP Hôpital Européen G. Pompidou	Paris	Ile-de-France
France	APHP Hôpital Lariboisière	Paris	Ile-de-France
France	APHP Hôpital Pitié-Salpêtrière - Service de Chirurgie	Paris	Ile-de-France
France	APHP Hôpital R. Debré	Paris	Ile-de-France
France	APHP Hôpital Saint Antoine	Paris	Ile-de-France
France	Hôpital Pitié-Salpêtrière - Service de Diabétologie	Paris	Ile-de-France
France	Hôpital René Dubos	Pontoise	Ile-de-France

Sponsors (1)

Lead Sponsor	Collaborator
Institut National de la Santé Et de la Recherche Médicale, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Secondary	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.	6 years
Secondary	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
Secondary	To define the phenotype of these lymphocytes.	As defined by exploratory analyses based on omics techniques.	6 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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