T1D Risk Assessment in Kids With Relatives

Assistance Publique - Hôpitaux de Paris512 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

SCREENING

Masking

NONE

Enrollment

512

Conditions

Type 1 Diabetes

Interventions

Analysis of early immune modificationsBIOLOGICAL

* 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

Collection of clinical and socio-demographic dataOTHER

1. Questionnaire filled in by clinicians at enrollment and at birth 2. Self-administered questionnaire filled by parents at enrollment, at birth, and then at month 8, 18, 30 and 42

Eligibility

Sex: ALLMin age: 1 Day

Medical Language ↔ Plain English

Inclusion Criteria: 1. 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 2. 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 3. 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

Locations (1)

Cochin Hospital

Paris, France

Outcomes

Primary Outcomes

Autoreactive T lymphocytes

presence, frequency, antigen specificity, phenotype

Time frame: 48 months

Secondary Outcomes

Metagenomic signatures

presence, frequency, type

Time frame: 48 months

Metabolic signatures

presence, frequency, type

Time frame: 48 months

Environmental factors

1. Sociodemographic characteristics, e.g. age, gender, occupation, living place, family situation, number of children, education, housing type, animal contact 2. Family history, e.g. autoimmune diseases 3. Personal history, e.g. diabetes characteristics, associated co-morbidities, obstetrical history 4. Clinical data

Time frame: 48 months

Incidence of autoantibodies

Presence, titer, specificity

Time frame: 48 months

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.