General Population Level Estimation for Type 1 Diabetes Risk in Children During Routine Care Delivery

Study Overview
=================
Brief Summary
-----------------
In partnership with Helmsley Charitable Trust, the Sanford PLEDGE Study is a large-scale, observational, feasibility study of general population screening for T1D and celiac autoantibodies. Screening is incorporated into routine health care visits within an integrated health system.

Detailed Description
-----------------
Most children with type 1 diabetes (T1D) do not have a family member with diabetes and often are not diagnosed until the child is very sick. Research suggests that screening and identifying children at risk for T1D autoantibodies can prevent serious illness at the time of diagnosis and improve long-term health outcomes. The investigators will screen children, ages 0-5.99 or 9-16 years for blood markers related to T1D and celiac disease during routine healthcare delivery at birth, 1, 2 and 5 years, or once between 9 and 16 years of age. Children with confirmed autoantibodies will be offered participation in other monitoring or prevention trials (T1D), or referred to clinical care (celiac).

Official Title
-----------------
Sanford Population Level Estimation of Type 1 Diabetes Risk GEnes in Children

Conditions
-----------------
Type 1 Diabetes, Celiac Disease

Intervention / Treatment
-----------------
* Diagnostic Test: Sera and whole blood sampling
* Diagnostic Test: Differential Gene Expression (DGE)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Newborn Entry: Viable, term infants, defined as 36 weeks gestation by either dates or ultrasound who are born to pregnant women, 18 years or older, who are willing and able to provide informed consent (IC) prior to the onset of active labor. Who are born at a Sanford Health Hospital and plan to have routine well-child care at a Sanford Clinic Pediatric Entry: Children less than 6 years of age who receive their routine care at a Sanford facility and whose parents are able to provide IC. Adolescent Entry: Children, ages 9-16 years old, who receive their routine care at a Sanford facility and whose parents are able to provide IC. Siblings of children known to have T1D-relevant antibodies; ages 6 to 17 years old who receive care at a Sanford clinic Have an active MyChart account (with proxy access). Exclusion Criteria: Subject is in the opinion of the investigator, unable to comply with the requirements of the study protocol. Children known to have T1D

Ages Eligible for Study
-----------------
Minimum Age: 0 Minutes
Maximum Age: 17 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Study Group<br>Children receiving routine care at a Sanford facility | Diagnostic Test: Sera and whole blood sampling<br>* Study Entry: Single Nucleotide Polymorphism (SNP)-Based Genetic Risk Score at study entry. 2 years old: T1D autoantibodies, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibodies 5 years old: T1D and celiac autoantibodies 9-16 year old: one-time T1D and celiac autoantibodies Siblings of people with T1D autoimmunity, ages 6-17 years: one-time T1D and celiac autoantibodies<br>Diagnostic Test: Differential Gene Expression (DGE)<br>* Opt-in: Differential Gene Expression from cord blood at birth and peripheral blood at 12 months of age<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Demonstrated feasibility of large-scale population screening, as evidenced by: | The percentage of parent(s) that viewed the MyChart study information who went on to complete the MyChart informed consent, HIPAA and questionnaires. Of those who consented to be in the study, the percentage who went on to obtain the initial sample. Of the total samples collected, percentage that were valid and results received. The percentage of subjects who complete their  60 month visit by their 6th birthday. | By year 10 of the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rates for T1D-relevant and celiac autoantibodies |  | By year 10 of study | 
| Percentage of T1D seropositive subjects who enroll in another T1D monitoring or prevention study. |  | By year 10 of study | 
| Percentage of celiac seropositive subjects referred on to GI or primary care |  | By year 10 of study | 
| The percentage of celiac seropositive subjects who were evaluated in clinical setting |  | By year 10 of study | 
| The rate of development of overt hyperglycemia consistent with T1D (Stage 3). |  | By year 10 of study | 
| Proportion of participants developing overt hyperglycemia consistent with T1D (Stage 3), who present in diabetic ketoacidosis (DKA) |  | By year 10 of study | 
| Number and type of procedure-related adverse events |  | By year 10 of study | 
| Assessment of costs associated with implementation of study compared to potential impacts on cost and quality of life. |  | By year 10 of study | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Population screening, Type 1 Diabetes, Celiac Disease, Autoantibodies, Prevention, Diabetic Ketoacidosis (DKA), Genetic Risk Score, Differential Gene Expression, Economic Modeling, Quality of Life, Feasibility, Pragmatic, T1D