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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes; Celiac Disease
• Intervention / Treatment: Diagnostic test: Sera and whole blood sampling; Diagnostic test: Differential Gene Expression (DGE)

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).

• Study Type: Observational
• Enrollment (Estimated): 33000

Contacts and Locations

• Study Contact: Name: Ann Mays, RN, CPN; Phone Number: 605-312-6052; Email: ann.mays@sanfordhealth.org

Study Locations

• United States
  • Minnesota
    • Bemidji, Minnesota, United States, 56601
      • Recruiting
      • Sanford Bemidji Region Clinics
      • Contact: Ann Mays, RN, CPN; Phone Number: 605-312-6052; Email: ann.mays@sanfordhealth.org
      • Principal Investigator: Kurt Griffin, PhD, MD
  • North Dakota
    • Bismarck, North Dakota, United States, 58501
      • Recruiting
      • Sanford Bismarck Region Clinics
      • Contact: Ann Mays, RN, CPN; Phone Number: 605-312-6052; Email: ann.mays@sanfordhealth.org
      • Principal Investigator: Kurt Griffin, PhD, MD
    • Fargo, North Dakota, United States, 58112
      • Recruiting
      • Sanford Fargo Region Clinics
      • Principal Investigator: Kurt Griffin, PhD, MD
      • Contact: Ann Mays; Phone Number: 605-312-6052; Email: ann.mays@sanfordhealth.org
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57105
      • Recruiting
      • Sanford Sioux Falls Region Clinics
      • Principal Investigator: Kurt Griffin, PhD, MD
      • Contact: Ann Mays; Phone Number: 605-312-6052; Email: ann.mays@sanfordhealth.org
      • Sub-Investigator: Sharon Hunt, BS, MS, MBA
      • Sub-Investigator: Candice Nelson, MD, FAAP
      • Sub-Investigator: Stephanie Hanson, MD, FAAP
      • Sub-Investigator: Louis Casas, MD, FAAP
      • Sub-Investigator: Brenda Thurlow, MD, FAAP
      • Sub-Investigator: Kyle Baum, MD
      • Sub-Investigator: Ann Mays, RN, CPN

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 17 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Children born at and/or followed at Sanford Health System facilities:

1. . 0-5 years of age;
2. . 9-16 years of age;
3. . Siblings of children known to have T1D-relevant antibodies, ages 6 to 17 years old.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Study Group; Children receiving routine care at a Sanford facility

Diagnostic test: Sera and whole blood sampling; 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; Diagnostic test: Differential Gene Expression (DGE); Opt-in: Differential Gene Expression from cord blood at birth and peripheral blood at 12 months of age

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	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

Collaborators and Investigators

• Sponsor: Sanford Health
• Collaborators: University of Exeter; The Leona M. and Harry B. Helmsley Charitable Trust; Pacific Northwest Research Institute
• Investigators: Principal Investigator: Kurt Griffin, PhD, MD, Sanford Research

Publications and helpful links

General Publications

• Sims EK, Besser REJ, Dayan C, Geno Rasmussen C, Greenbaum C, Griffin KJ, Hagopian W, Knip M, Long AE, Martin F, Mathieu C, Rewers M, Steck AK, Wentworth JM, Rich SS, Kordonouri O, Ziegler AG, Herold KC; NIDDK Type 1 Diabetes TrialNet Study Group. Screening for Type 1 Diabetes in the General Population: A Status Report and Perspective. Diabetes. 2022 Apr 1;71(4):610-623. doi: 10.2337/dbi20-0054.

Helpful Links

• Sims et al.

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Estimated): March 1, 2031
• Study Completion (Estimated): March 1, 2031

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 17, 2020
• First Posted (Actual): July 20, 2020

Study Record Updates

• Last Update Posted (Actual): April 22, 2024
• Last Update Submitted That Met QC Criteria: April 19, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: Feasibility; Quality of Life; Prevention; Type 1 Diabetes; T1D; Population screening; Autoantibodies; Celiac Disease; Genetic Risk Score; Pragmatic; Diabetic Ketoacidosis (DKA); Differential Gene Expression; Economic Modeling
• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Malabsorption Syndromes; Diabetes Mellitus; Diabetes Mellitus, Type 1; Celiac Disease
• Other Study ID Numbers: PLEDGE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified patient characteristics, clinical and laboratory outcomes will be shared in an online platform.
• IPD Sharing Time Frame: Data will be available no later than 12 months after the conclusion of study.
• IPD Sharing Access Criteria: Data available to researchers approved by investigators.
• IPD Sharing Supporting Information Type: ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No