TrialNet Pathway to Prevention of T1D

Diabetes Mellitus, Type 1 Clinical Trial

Official title:

TrialNet Pathway to Prevention of T1D

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00097292
• Other study ID #: NHStudy (IND)
• Secondary ID: UC4DK117009UC4DK
• Status: Recruiting
• Start date: February 2004
• Est. completion date: July 2025

Study information

• Verified date: December 2023
• Source: University of South Florida
• Contact: TrialNet Central Information Center general info
• Phone: 1-800-425-8361
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 75000
• Est. completion date: July 2025
• Est. primary completion date: July 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Months to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Locations

Country	Name	City	State
Australia	Walter and Eliza Hall Institute	Parkville	Victoria
Canada	The Hospital for Sick Children	Toronto	Ontario
Finland	University of Turku	Turku
Italy	Vita-Salute San Raffaele University	Milan
United Kingdom	University of Bristol	Bristol
United States	Emory Children's Center	Atlanta	Georgia
United States	Joslin Diabetes Center	Boston	Massachusetts
United States	University of Texas Medical Center at Dallas	Dallas	Texas
United States	Barbara Davis Center for Childhood Diabetes	Denver	Colorado
United States	University of Florida	Gainesville	Florida
United States	Baylor College of Medicine	Houston	Texas
United States	Riley Hospital for Children, Indiana University	Indianapolis	Indiana
United States	The Children's Mercy Hospital	Kansas City	Missouri
United States	University of Minnesota	Minneapolis	Minnesota
United States	Vanderbilt University	Nashville	Tennessee
United States	Yale University School of Medicine	New Haven	Connecticut
United States	Columbia University	New York	New York
United States	Childrens Hospital of Orange County	Orange	California
United States	Children's Hospital of Pittsburgh of UPMC	Pittsburgh	Pennsylvania
United States	University of California San Francisco	San Francisco	California
United States	Benaroya Research Institute	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (5)

Lead Sponsor	Collaborator
University of South Florida	American Diabetes Association, National Center for Research Resources (NCRR), National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Finland,  Italy,  United Kingdom, 

References & Publications (5)

Atkinson MA, Eisenbarth GS. Type 1 diabetes: new perspectives on disease pathogenesis and treatment. Lancet. 2001 Jul 21;358(9277):221-9. doi: 10.1016/S0140-6736(01)05415-0. Erratum In: Lancet. 2001 Sep 1;358(9283):766. — View Citation

Bingley PJ, Christie MR, Bonifacio E, Bonfanti R, Shattock M, Fonte MT, Bottazzo GF, Gale EA. Combined analysis of autoantibodies improves prediction of IDDM in islet cell antibody-positive relatives. Diabetes. 1994 Nov;43(11):1304-10. doi: 10.2337/diab.43.11.1304. — View Citation

Diabetes Prevention Trial--Type 1 Diabetes Study Group. Effects of insulin in relatives of patients with type 1 diabetes mellitus. N Engl J Med. 2002 May 30;346(22):1685-91. doi: 10.1056/NEJMoa012350. — View Citation

Gale EA, Bingley PJ, Emmett CL, Collier T; European Nicotinamide Diabetes Intervention Trial (ENDIT) Group. European Nicotinamide Diabetes Intervention Trial (ENDIT): a randomised controlled trial of intervention before the onset of type 1 diabetes. Lancet. 2004 Mar 20;363(9413):925-31. doi: 10.1016/S0140-6736(04)15786-3. — View Citation

Verge CF, Gianani R, Kawasaki E, Yu L, Pietropaolo M, Jackson RA, Chase HP, Eisenbarth GS. Prediction of type I diabetes in first-degree relatives using a combination of insulin, GAD, and ICA512bdc/IA-2 autoantibodies. Diabetes. 1996 Jul;45(7):926-33. doi: 10.2337/diab.45.7.926. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Development of type 1 diabetes	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.	Monitoring is provided once or twice annually depending on risk level
Secondary	Metabolic and Autoantibody Assessments	Oral Glucose Tolerance Test (OGTT) HbA1c Autoantibodies: ICA, IA-2A, GAD65A, mIAA, ZnT8A	Metabolic and Autoantibody assessments are provided once or twice annually depending on risk level

External Links

•   American Diabetes Association
•   Juvenile Diabetes Research Foundation International
•   TrialNet Study Group
•   Type 1 Diabetes Clinical Trials