TrialNet Pathway to Prevention of T1D

NCT00097292 | Recruiting DMC

• 3 other identifiers: NHStudy (IND)UC4DK117009UC4DK106993
• Study Type: observational
• Target: 75,000
• Locations: 6 countries
• Sites: 22

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.

Conditions

Diabetes Mellitus, Type 1

Keywords

"at risk" for developing type 1 diabetes; T1DM; T1D; juvenile diabetes; Type 1 Diabetes TrialNet; TrialNet

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Metabolic and Autoantibody Assessments

  Metabolic and Autoantibody assessments are provided once or twice annually depending on risk level

Study Arms (2)

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

Eligibility Criteria

• Age: 2 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Probability Sample

Study Population

First and second/third degree relatives of individuals with type 1 diabetes.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of South Florida: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator
• American Diabetes Association: collaborator
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• National Center for Research Resources (NCRR): collaborator

Study Sites (22)

Childrens Hospital of Orange County

Orange, California, 92868, United States

RECRUITING

University of California San Francisco

San Francisco, California, 94143-0434, United States

RECRUITING

Stanford University Medical Center

Stanford, California, 94305-5208, United States

RECRUITING

Barbara Davis Center for Childhood Diabetes

Denver, Colorado, 80262, United States

RECRUITING

Yale University School of Medicine

New Haven, Connecticut, 06519, United States

RECRUITING

University of Florida

Gainesville, Florida, 32601-0296, United States

RECRUITING

Emory Children's Center

Atlanta, Georgia, 30322, United States

RECRUITING

Riley Hospital for Children, Indiana University

Indianapolis, Indiana, 46202, United States

RECRUITING

Joslin Diabetes Center

Boston, Massachusetts, 02215, United States

RECRUITING

University of Minnesota

Minneapolis, Minnesota, 58944, United States

RECRUITING

The Children's Mercy Hospital

Kansas City, Missouri, 64111, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

Children's Hospital of Pittsburgh of UPMC

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Vanderbilt University

Nashville, Tennessee, 37232, United States

RECRUITING

University of Texas Medical Center at Dallas

Dallas, Texas, 75390-8858, United States

RECRUITING

Baylor College of Medicine

Houston, Texas, 77030, United States

RECRUITING

Benaroya Research Institute

Seattle, Washington, 98101-2795, United States

RECRUITING

Walter and Eliza Hall Institute

Parkville, Victoria, 3050, Australia

RECRUITING

The Hospital for Sick Children

Toronto, Ontario, M5G-1x8, Canada

RECRUITING

University of Turku

Turku, FIN-20520, Finland

SUSPENDED

Vita-Salute San Raffaele University

Milan, +39-02-2643 2818, Italy

SUSPENDED

University of Bristol

Bristol, BS10 5NB UK, United Kingdom

SUSPENDED

Related Publications (11)

• 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.

  PMID: 12037147 BACKGROUND

• 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.

  PMID: 15043959 BACKGROUND

• 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.

  PMID: 11476858 BACKGROUND

• 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.

  PMID: 8666144 BACKGROUND

• 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.

  PMID: 7926304 BACKGROUND

• Martinenghi S, Merolla A, Grogan P, Bianconi E, Senni E, Goncharova A, Massara F, Ragogna F, Bazzigaluppi E, Pastore MR, Bonfanti R, Bosi E. Prevention of diabetic ketoacidosis in relatives screened for islet autoantibodies and followed up in the TrialNet Pathway to Prevention study at a single institution in Italy. Diabetologia. 2025 Sep;68(9):1889-1898. doi: 10.1007/s00125-025-06461-z. Epub 2025 May 29.

  PMID: 40439773 DERIVED

• Triolo TM, Pyle L, Broncucia H, Armstrong T, Yu L, Gottlieb PA, Steck AK. Association of High-Affinity Autoantibodies With Type 1 Diabetes High-Risk HLA Haplotypes. J Clin Endocrinol Metab. 2022 Mar 24;107(4):e1510-e1517. doi: 10.1210/clinem/dgab853.

  PMID: 34850014 DERIVED

• Evans-Molina C, Sims EK, DiMeglio LA, Ismail HM, Steck AK, Palmer JP, Krischer JP, Geyer S, Xu P, Sosenko JM; Type 1 Diabetes TrialNet Study Group. beta Cell dysfunction exists more than 5 years before type 1 diabetes diagnosis. JCI Insight. 2018 Aug 9;3(15):e120877. doi: 10.1172/jci.insight.120877. eCollection 2018 Aug 9.

  PMID: 30089716 DERIVED

• Ferrara CT, Geyer SM, Evans-Molina C, Libman IM, Becker DJ, Wentworth JM, Moran A, Gitelman SE, Redondo MJ; Type 1 Diabetes TrialNet Study Group. The Role of Age and Excess Body Mass Index in Progression to Type 1 Diabetes in At-Risk Adults. J Clin Endocrinol Metab. 2017 Dec 1;102(12):4596-4603. doi: 10.1210/jc.2017-01490.

  PMID: 29092051 DERIVED

• Bosi E, Boulware DC, Becker DJ, Buckner JH, Geyer S, Gottlieb PA, Henderson C, Kinderman A, Sosenko JM, Steck AK, Bingley PJ; Type 1 Diabetes TrialNet Study Group. Impact of Age and Antibody Type on Progression From Single to Multiple Autoantibodies in Type 1 Diabetes Relatives. J Clin Endocrinol Metab. 2017 Aug 1;102(8):2881-2886. doi: 10.1210/jc.2017-00569.

  PMID: 28531305 DERIVED

• Herold KC, Usmani-Brown S, Ghazi T, Lebastchi J, Beam CA, Bellin MD, Ledizet M, Sosenko JM, Krischer JP, Palmer JP; Type 1 Diabetes TrialNet Study Group. beta cell death and dysfunction during type 1 diabetes development in at-risk individuals. J Clin Invest. 2015 Mar 2;125(3):1163-73. doi: 10.1172/JCI78142. Epub 2015 Feb 2.

  PMID: 25642774 DERIVED

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, serum, plasma

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Kevan Herold, M.D.

  Yale University

  STUDY CHAIR

Central Study Contacts

TrialNet Central Information Center general info

CONTACT

1-800-425-8361

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2004
• First Posted: November 22, 2004
• Study Start: February 1, 2004
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2030
• Last Updated: July 1, 2025

Record last verified: 2025-06

Locations

FI (1); AU (1); IT (1); US (17); GB (1); CA (1)