T1D Risk Assessment in Kids With Relatives (TRAKR)

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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Biological: Analysis of early immune modifications; Other: Collection of clinical and socio-demographic data

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.

• Study Type: Interventional
• Enrollment (Actual): 512
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Paris, France, 75014
    • Cochin Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Children born to mother/father with type 1 diabetes

Biological: Analysis of early immune modifications; 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; Other: Collection of clinical and socio-demographic data; 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

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

Collaborators and Investigators

• Sponsor: Assistance Publique - Hôpitaux de Paris
• Collaborators: Commissariat A L'energie Atomique; Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement; Institut National de la Santé et de la Recherche Médicale (INSERM) U1016 - Institut Cochin, Immunology of Diabetes Team, Paris, France; INSERM U1153, Epidemiology Research Unit on Perinatal Health and Women and Children Health, Port-Royal Hospital, Paris, France
• Investigators: Principal Investigator: Roberto Mallone, M.D, Ph.D., INSERM U1016

Study record dates

Study Major Dates

• Study Start (Actual): May 28, 2015
• Primary Completion (Actual): May 17, 2019
• Study Completion (Actual): May 17, 2019

Study Registration Dates

• First Submitted: July 3, 2014
• First Submitted That Met QC Criteria: July 8, 2014
• First Posted (Estimate): July 9, 2014

Study Record Updates

• Last Update Posted (Actual): April 5, 2021
• Last Update Submitted That Met QC Criteria: April 2, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: children; relatives; Type 1 diabetes; risk assessment; autoantibodies; T cells; lymphocytes; immunological marker; epitopes; Children born to mother/father with type 1 diabetes and their parents
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1
• Other Study ID Numbers: P130405; ID RCB : 2014-A00453-44

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO