T1D Risk Assessment in Kids With Relatives

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine whether early immunological markers (activation of autoreactive T lymphocytes) precede and are predictive of the appearance of autoantibodies in children born from type 1 diabetic parents.

Detailed Description
-----------------
The prevalence of type 1 diabetes (T1D) is estimated between 0.2 and 0.4% in France. The incidence in France is more than 10/105 per year, with a steady increase ( 4%/year), especially in children. Infants born to parents with T1D have a 15-fold higher risk to develop T1D compared to the general population. The appearance of autoantibodies precedes and is highly predictive of the later occurrence of T1D. The activation of B lymphocytes, which produce autoantibodies, is controlled by T helper lymphocytes. Hence, biomarkers associated with initial T lymphocyte activation are likely to precede the appearance of autoantibodies. The aim of the TRAKR study is to determine whether the appearance of autoreactive T lymphocytes is predictive of the emergence of autoantibodies. The secondary objectives are: 1) to evaluate whether metagenomic, metabolic, or environmental factors are associated with the appearance of autoantibodies; 2) to evaluate the incidence and the time of autoantibody appearance in a French population of genetically at-risk children; 3) to compare the incidence of autoantibodies between infants born to T1D fathers and mothers.

Official Title
-----------------
Early Immunological, Metagenomic, Metabolic and Environmental Factors in the Progression to Type 1 Diabetes: the TRAKR Cohort

Conditions
-----------------
Type 1 Diabetes

Intervention / Treatment
-----------------
* Biological: Analysis of early immune modifications
* Other: Collection of clinical and socio-demographic data


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Mother and/or father with type 1 diabetes age > 18 years type 1 diabetes : insulin-dependent diabetes positive for autoantibodies against insulin and/or GAD and/or IA-2 and/or ZnT8 at the time of diagnosis planning to give birth or having given birth since less than 8 months agreeing to participate upon written informed consent covered by the French social security system Mother/father without Type 1 diabetes age > 18 years old with a spouse with type 1 diabetes : insulin-dependent diabetes positive for autoantibodies against insulin and/or GAD and/or IA-2 and/or ZnT8 at the time of diagnosis planning to give birth or having given birth since less than 8 months agreeing to participate upon written informed consent covered by the French social security system Children born to mother and/or father with type 1 diabetes age < 8 months with at least one parent with T1D with both parents agreeing to participate both parents covered by the French social security system Exclusion Criteria: 1) Mother/father secondary forms of diabetes monogenic forms of diabetes 1 or 2) For the mother malignant neoplastic or psychiatric disease 3 ) Newborns of mother/father with type 1 diabetes Severe foetal disease Severe congenital malformation Congenital measles

Ages Eligible for Study
-----------------
Minimum Age: 1 Day

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Children born to mother/father with type 1 diabetes<br> | Biological: Analysis of early immune modifications<br>* blood and stool sampling in parents during pregnancy (at enrollment, i.e. 7th-8th month of pregnancy) cord blood sampling stool sampling in mothers and newborns at birth (day 7) blood and stool sampling in children at the age of 8, 18, 30 and 42 months<br>Other: Collection of clinical and socio-demographic data<br>* Questionnaire filled in by clinicians at enrollment and at birth Self-administered questionnaire filled by parents at enrollment, at birth, and then at month 8, 18, 30 and 42<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Autoreactive T lymphocytes | presence, frequency, antigen specificity, phenotype | 48 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Metagenomic signatures | presence, frequency, type | 48 months | 
| Metabolic signatures | presence, frequency, type | 48 months | 
| Environmental factors | Sociodemographic characteristics, e.g. age, gender, occupation, living place, family situation, number of children, education, housing type, animal contact Family history, e.g. autoimmune diseases Personal history, e.g. diabetes characteristics, associated co-morbidities, obstetrical history Clinical data | 48 months | 
| Incidence of autoantibodies | Presence, titer, specificity | 48 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Type 1 diabetes, risk assessment, immunological marker, children, relatives, autoantibodies, lymphocytes, T cells, epitopes, Children born to mother/father with type 1 diabetes and their parents