TrialNet Pathway to Prevention of T1D

Sponsor

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT00097292

Collaborator

National Institute of Allergy and Infectious Diseases (NIAID) (NIH), National Center for Research Resources (NCRR) (NIH), American Diabetes Association (Other)

75,000

Enrollment

Locations

257

Duration (Months)

3409.1

Patients Per Site

13.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Rationale:

The accrual of data from the laboratory and from epidemiologic and prevention trials has improved the understanding of the etiology and pathogenesis of type 1 diabetes mellitus (T1DM). Genetic and immunologic factors play a key role in the development of T1DM, and characterization of the early metabolic abnormalities in T1DM is steadily increasing. However, information regarding the natural history of T1DM remains incomplete. The TrialNet Natural History Study of the Development of T1DM (Pathway to Prevention Study) has been designed to clarify this picture, and in so doing, will contribute to the development and implementation of studies aimed at prevention of and early treatment in T1DM.

Purpose:

TrialNet is an international network dedicated to the study, prevention, and early treatment of type 1 diabetes. TrialNet sites are located throughout the United States, Canada, Finland, United Kingdom, Italy, Germany, Sweden, Australia, and New Zealand. TrialNet is dedicated to testing new approaches to the prevention of and early intervention for type 1 diabetes.

The goal of the TrialNet Natural History Study of the Development of Type 1 Diabetes is to enhance our understanding of the demographic, immunologic, and metabolic characteristics of individuals at risk for developing type 1 diabetes.

The Natural History Study will screen relatives of people with type 1 diabetes to identify those at risk for developing the disease. Relatives of people with type 1 diabetes have about a 5% percent chance of being positive for the antibodies associated with diabetes. TrialNet will identify adults and children at risk for developing diabetes by testing for the presence of these antibodies in the blood. A positive antibody test is an early indication that damage to insulin-secreting cells may have begun. If this test is positive, additional testing will be offered to determine the likelihood that a person may develop diabetes. Individuals with antibodies will be offered the opportunity for further testing to determine their risk of developing diabetes over the next 5 years and to receive close monitoring for the development of diabetes.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1

Detailed Description

Detailed Description:

The Pathway to Prevention Study is conducted in two parts:

Screening
Monitoring (annual and semi-annual depending on risk)

In Screening , a simple blood test is done to screen for the presence of diabetes-related biochemical autoantibodies (GAD and mIAA). Additional autoantibodies ICA, IA-2A, and ZnT8A will also measured in individuals positive for mIAA. ICA, IA-2A, and ZnT8A will be measured in individuals positive for GAD. Participants can go to a TrialNet Clinical Center, Affiliate, or request a screening kit to have their blood drawn by a local physician or laboratory. Participants will be provided with their screening results within 4-6 weeks.

If autoantibodies are present, participants will be invited to have additional testing to determine their average risk of developing diabetes over the next 5 years. Participants that are single autoantibody positive will be re-tested annually for the development of multiple autoantibodies. Multiple autoantibody positive participants will undergo an eligibility visit which will include an Oral Glucose Tolerance Test (OGTT), re-testing for biochemical and islet cell autoantibodies if needed, and measurement of HbA1c.

Multiple autoantibody positive individuals with a normal glucose tolerance and an HbA1c < 6.0% will be asked to come for follow-up on annual basis; multiple autoantibody positive individuals with an abnormal glucose tolerance or an HbA1c ≥ 6.0%will be asked to come for follow-up visits on semi-annual basis.

Participants will be monitored for possible progression towards type 1 diabetes and may be offered the opportunity to enter into a prevention study such (e.g., Oral Insulin prevention study) or an early treatment study if they are diagnosed with type 1 diabetes while participating in the Natural History Study.

Study Design

Study Type:

Observational

Anticipated Enrollment :

75000 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

TrialNet Pathway to Prevention of T1D

Study Start Date :

Feb 1, 2004

Anticipated Primary Completion Date :

Jul 1, 2025

Anticipated Study Completion Date :

Jul 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Annual Re-Testing/Annual Metabolic Monitoring Participants will be monitored annually for risk of type 1 diabetes.
Semi-Annual Metabolic Monitoring Participants will be monitored every six months for risk of type 1 diabetes

Outcome Measures

Primary Outcome Measures

Development of type 1 diabetes [Monitoring is provided once or twice annually depending on risk level]
The primary outcome is the development of diabetes as defined by the American Diabetes Association (ADA) based on glucose testing, or the presence of symptoms and unequivocal hyperglycemia.

Secondary Outcome Measures

Metabolic and Autoantibody Assessments [Metabolic and Autoantibody assessments are provided once or twice annually depending on risk level]
Oral Glucose Tolerance Test (OGTT) HbA1c Autoantibodies: ICA, IA-2A, GAD65A, mIAA, ZnT8A

Eligibility Criteria

Criteria

Ages Eligible for Study:

30 Months to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Individuals 2.5 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
Individuals 2.5-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
Individuals 2.5-45 years old without a type 1 diabetes proband, who are known to have 1 or more islet antibody are eligible for screening if needed to determine eligibility for a clinical trial to delay or prevent disease progression.

Exclusion Criteria:

To be eligible a person must not:

Have diabetes already
Have a previous history of being treated with insulin or oral diabetes medications.
Currently be using systemic immunosuppressive agents (topical and inhaled agents are acceptable)
Have any known serious diseases

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Childrens Hospital of Orange County	Orange	California	United States	92868
2	University of California San Francisco	San Francisco	California	United States	94143-0434
3	Stanford University Medical Center	Stanford	California	United States	94305-5208
4	Barbara Davis Center for Childhood Diabetes	Denver	Colorado	United States	80262
5	Yale University School of Medicine	New Haven	Connecticut	United States	06519
6	University of Florida	Gainesville	Florida	United States	32601-0296
7	Emory Children's Center	Atlanta	Georgia	United States	30322
8	Riley Hospital for Children, Indiana University	Indianapolis	Indiana	United States	46202
9	Joslin Diabetes Center	Boston	Massachusetts	United States	02215
10	University of Minnesota	Minneapolis	Minnesota	United States	58944
11	The Children's Mercy Hospital	Kansas City	Missouri	United States	64111
12	Columbia University	New York	New York	United States	10032
13	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania	United States	15213
14	Vanderbilt University	Nashville	Tennessee	United States	37232
15	University of Texas Medical Center at Dallas	Dallas	Texas	United States	75390-8858
16	Baylor College of Medicine	Houston	Texas	United States	77030
17	Benaroya Research Institute	Seattle	Washington	United States	98101-2795
18	Walter and Eliza Hall Institute	Parkville	Victoria	Australia	3050
19	The Hospital for Sick Children	Toronto	Ontario	Canada	M5G-1x8
20	University of Turku	Turku		Finland	FIN-20520
21	Vita-Salute San Raffaele University	Milan		Italy	+39-02-2643 2818
22	University of Bristol	Bristol		United Kingdom	BS10 5NB UK