Screening for Islet Autoantibodies in the Israeli Paediatric General Population for Detection of Pre-symptomatic Type-1 Diabetes Mellitus

Study Overview
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Brief Summary
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A national screening program for children aged 9-18 months that will be tested for the presence of islet autoantibodies.Up to 50,000 Children will be screened by their primary care physician all over Israel. The initial screening will be done at the age of 1 year (in conjunction with the routinely collection of blood for CBC ) and repeated at ages 2-5 years. Antibodies will be measured in capillary blood samples using the Ultrasensitive Antibody Detection by Agglutination-PCR (ADAP) technology developed by Enable Biosciences, which is 1,000-10,000 times more analytically sensitive than currently used methods. By using this innovative technology in such a large cohort, the study is anticipated to detect antibodies at an unprecedented earlier age.When positive in the screening, multiple antibodies will be confirmed by a second sample analyzed by the ADAP technology. In addition, multiple antibodies will be also measured using a radio-binding assay (RBA) of a venous blood sample for investigational purpose only. Children with confirmed multiple antibodies (stage 1 or 2 T1D) will be followed up routinely for the appearance of clinical signs of diabetes (HbA1c, repeated OGTT, monitoring of urine and blood glucose where indicated) and will be invited along with their families to attend an educational program. This program will include diabetes education emphasizing on DKA prevention as well as stress assessment for the families involved and stress alleviating interventions. The analysis and storage of the samples will be done in a single screening center at Schneider Children's Medical Center of Israel.

Official Title
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Screening for Islet Autoantibodies in the Israeli Paediatric General Population for Detection of Pre-symptomatic Type-1 Diabetes Mellitus

Conditions
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Type1diabetes

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained before any trial-related activities Children aged 9-18 months at first screening. Exclusion Criteria: Known diagnosis of diabetes (Type 1 or other)

Ages Eligible for Study
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Minimum Age: 9 Months
Maximum Age: 18 Months

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Negative result at the first autoantibodies screening test<br>Participants will be invited to repeat the screening test at the age of 2-5 years old | |
| Positive result at the first or second autoantibodies screening test<br>Participants will be monitored annually for risk of type 1 diabetes. (HbA1c, repeated OGTT, monitoring of urine and blood glucose where indicated) Families will attend diabetes-educational program emphasizing on DKA prevention Stress assessment for the families involved and stress alleviating interventions when required. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Diagnosis of presymptomatic type 1 diabetes | Presymptomatic type 1 diabetes, defined as positive for 2 or more islet autoantibodies (GADA, IA-2A, and IAA) or those with high levels of a single antibody in both the screening and confirmation samples or in the screening sample plus a diagnosis of diabetes prior to obtaining the conformation sample. Presymptomatic type 1 diabetes will be classified as stage 1, 2, or 3: Stage 1 will be defined as 2 or more islet autoantibodies or high levels of a single antibody and normal glucose tolerance based on OGTT results. (not including patients with only a single antibody who have first degree relative with type 1 diabetes) Stage 2 will be defined as 1 or more islet autoantibodies accompanied by dysglycemia (fasting plasma glucose of 110-125 mg/dL or impaired 2-hour plasma glucose of 140- 199 mg/dL and/or plasma glucose ≥200 mg/dL at intermediate time points [30, 60, 90 minutes]) based on OGTT results. Stage 3 will be defined according to the American Diabetes Association criteria | End of screening and follow-up period-4 years after obtaining the first screening test | 
| Frequency of Diabetic Ketoacidosis on the clinical presentation of Type 1 Diabetes |  | End of screening and follow-up period-4 years after obtaining the first screening test | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The average age of islet autoantibody seroconversion |  | End of screening and follow-up period-4 years after obtaining the first screening test | 
| The rate of islet autoantibody seroconversion |  | End of screening and follow-up period-4 years after obtaining the first screening test | 
| The rate of progression from pre-symptomatic T1D to clinical diabetes |  | End of screening and follow-up period-4 years after obtaining the first screening test | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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autoantibodies screening