Clinical trial NCT02184676: T1D Risk Assessment in Kids With Relatives
Official title: Early Immunological, Metagenomic, Metabolic and Environmental Factors in the Progression to Type 1 Diabetes: the TRAKR Cohort
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: 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
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Institut National de la Santé et de la Recherche Médicale (INSERM) U1016 - Institut Cochin, Immunology of Diabetes Team, Paris, France
name: INSERM U1153, Epidemiology Research Unit on Perinatal Health and Women and Children Health, Port-Royal Hospital, Paris, France
name: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
name: Commissariat A L'energie Atomique
First posted: 2014-07-09
Enrollment: 512
Sex: ALL
Minimum age (years): 1
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: SCREENING

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.

Eligibility criteria: 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

Primary outcomes:
measure: Autoreactive T lymphocytes
timeFrame: 48 months
Secondary outcomes:
measure: Metagenomic signatures
timeFrame: 48 months
measure: Metabolic signatures
timeFrame: 48 months
measure: Environmental factors
timeFrame: 48 months
measure: Incidence of autoantibodies
timeFrame: 48 months
Other outcomes:
Locations:
city: Paris
country: France
facility: Cochin Hospital
Study officials:
affiliation: INSERM U1016
name: Roberto Mallone, M.D, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: