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TrialNet Pathway to Prevention of T1D

Recruiting
Conditions
Diabetes Mellitus, Type 1
Registration Number
NCT00097292
Lead Sponsor
University of South Florida
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.

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.

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
75000
Inclusion Criteria
  • Individuals 2 to 45 years old who have an immediate family member with type 1 diabetes (such as a child, parent, or sibling)
  • Individuals 2-20 years old who have an extended family member with type 1 diabetes (such as a cousin, niece, nephew, aunt, uncle, grandparent, or half-sibling)
  • Those aged 2 years to 45 years who are not family members and are known to have 1 or more islet antibodies
Exclusion Criteria

To be eligible a person must not:

  • Have diabetes already
  • Have previous or current use of medications for the control of hyperglycemia/diabetes.
  • Currently be using immunosuppressive or immunomodulatory agents (topical and inhaled agents are acceptable)
  • Have known severe active diseases, and/or diseases which are likely to limit life expectancy or lead to the use of chronic immunosuppressive or immunomodulatory therapies during the course of the study

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Development of type 1 diabetesMonitoring 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
NameTimeMethod
Metabolic and Autoantibody AssessmentsMetabolic 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

Trial Locations

Locations (22)

The Hospital for Sick Children

🇨🇦

Toronto, Ontario, Canada

Baylor College of Medicine

🇺🇸

Houston, Texas, United States

Benaroya Research Institute

🇺🇸

Seattle, Washington, United States

University of California San Francisco

🇺🇸

San Francisco, California, United States

Barbara Davis Center for Childhood Diabetes

🇺🇸

Denver, Colorado, United States

University of Minnesota

🇺🇸

Minneapolis, Minnesota, United States

Vanderbilt University

🇺🇸

Nashville, Tennessee, United States

Joslin Diabetes Center

🇺🇸

Boston, Massachusetts, United States

Emory Children's Center

🇺🇸

Atlanta, Georgia, United States

Riley Hospital for Children, Indiana University

🇺🇸

Indianapolis, Indiana, United States

Columbia University

🇺🇸

New York, New York, United States

Childrens Hospital of Orange County

🇺🇸

Orange, California, United States

Stanford University Medical Center

🇺🇸

Stanford, California, United States

Children's Hospital of Pittsburgh of UPMC

🇺🇸

Pittsburgh, Pennsylvania, United States

University of Turku

🇫🇮

Turku, Finland

Vita-Salute San Raffaele University

🇮🇹

Milan, Italy

University of Bristol

🇬🇧

Bristol, United Kingdom

University of Texas Medical Center at Dallas

🇺🇸

Dallas, Texas, United States

Walter and Eliza Hall Institute

🇦🇺

Parkville, Victoria, Australia

Yale University School of Medicine

🇺🇸

New Haven, Connecticut, United States

University of Florida

🇺🇸

Gainesville, Florida, United States

The Children's Mercy Hospital

🇺🇸

Kansas City, Missouri, United States

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