Clinical trial NCT00279318: TEDDY - The Environmental Determinants of Diabetes in the Young
Official title: Consortium for Identification of Environmental Triggers of Type 1 Diabetes
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Type 1 Diabetes Mellitus
Keywords: Environment
Exposures
Diet
Toxins
Psychosocial
Infectious Agents
Bacterial
Viral
Immunizations
Autoantibody
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institute of Environmental Health Sciences (NIEHS)
name: Juvenile Diabetes Research Foundation
name: Centers for Disease Control and Prevention
First posted: 2006-01-19
Enrollment: 8667
Sex: ALL
Minimum age (years): 0
Maximum age (years): 4
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Childen up to 4 months of age with specified HLA are enrolled and followed longitudnally until 15 years of age

Brief summary: The long-term goal of the TEDDY study is the identification of infectious agents, dietary factors, or other environmental agents, including psychosocial factors which trigger T1DM in genetically susceptible individuals or which protect against the disease. Identification of such factors will lead to a better understanding of disease pathogenesis and result in new strategies to prevent, delay or reverse T1DM.

Detailed description: Epidemiologic patterns suggest that viruses, nutrition, toxic agents or socioeconomic psychosocial factors may contribute to the etiology alone or in combination. Elucidation is confounded by the long interval between exposure and onset of clinical disease, as well as the interaction of multiple genes and/or insults, which appear to interact in a complex manner. Numerous studies have investigated environmental influences but have yielded conflicting results. This may be in part due to the failure to account for genetic susceptibility, begin observation at early ages or in utero, and/or monitor subjects long term and frequently.

Hypotheses:

1. Initiation of persistent beta-cell autoimmunity and progression from beta-cell autoimmunity to diabetes is increased with:

   1. Exposure to a trigger factor during pregnancy, such as infections, preeclampsia, blood incompatibility, or birth weight.
   2. Differences in the timing of the introduction and/or the type of dietary constituents that include exposure to cereals or gluten, exposure to cow's milk during infancy and/or childhood, and short duration of breast- feeding;
   3. Lower intake of serum 25 hydroxyvitamin D in early infancy, vitamin E, anti-oxidants (e.g., carotenoids, ascorbic acid, selenium, or omega-3 fatty acids);
   4. Higher frequency of specific (e.g., enterovirus, rotavirus, or bacterial) infections, or non-specific childhood infections including those that exhibit molecular mimicry;
   5. Increased exposure to routine childhood immunizations and their timing;
   6. Environmental factors that may be contained in drinking water (e.g., low concentrations of zinc or high concentrations of nitrates, or lower pH levels);
   7. Exposure to household pets, and various allergies;
   8. Excessive weight gain;
   9. Increased psychological stress.
2. The risk of persistent beta-cell autoimmunity is lower in children from the general population than in offspring or siblings of T1DM patients when stratifying for the HLA DR-DQ genotype and exposure to environmental triggers.
3. The interaction of HLA DR-DQ genotype with exposure to dietary or infectious factors leads to increased incidence of beta-cell autoimmunity and T1DM.
4. We expect that in some families study participation will be associated with affective (anxiety, depression) and behavioral responses (e.g. actions to prevent possible T1DM).

Eligibility criteria: Inclusion Criteria:

* Newborns with high risk HLA in the general population or having a first- degree relative affected with T1DM
* Newborns are less than 4 months of age

Exclusion Criteria:

* Have an illness or birth defect that precludes long-term follow-up or involves use of treatment that may alter the natural history of diabetes (e.g. steroids or insulin)
* Refuses to have blood and stool samples stored at the NIDDK Repository

Primary outcomes:
measure: Appearance of one or more islet cell autoantibodies: GADA, IAA, or IA-2A confirmed at two consecutive visits.
timeFrame: September 2025
Secondary outcomes:
measure: Development of T1DM
timeFrame: September 2025
Other outcomes:
Locations:
city: Denver
country: United States
facility: University of Colorado Health Sciences Center
state: Colorado
city: Gainesville
country: United States
facility: Augusta University
state: Florida
city: Augusta
country: United States
facility: Augusta University
state: Georgia
city: Seattle
country: United States
facility: Pacific Northwest Research Institute
state: Washington
city: Turku
country: Finland
facility: Wellbeing Services County of Southwest Finland
city: Munich
country: Germany
facility: Diabetes Research Institute
city: Malmo
country: Sweden
facility: Lund University
Study officials:
affiliation: University of South Florida
name: Jeffrey P. Krischer, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Colorado Health Science Center
name: Marian J. Rewers, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Pacific Northwest Research Institute
name: William A. Hagopian, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lund University
name: Ake Lernmark, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wellbeing Services County of Southwest Finland
name: Jorma Toppari, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Augusta University Research Institute, Inc.
name: Richard McIndoe, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Diabetes Research Institute
name: Anette G. Ziegler, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: National Institutes of Diabetes and Digestive Kidney Diseases
name: Beena Akolkar, PhD
role: STUDY_DIRECTOR
References:
citation: Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ, She JX, Toppari J, Ziegler AG, Akolkar B; TEDDY Study Group. Predictors of the Initiation of Islet Autoimmunity and Progression to Multiple Autoantibodies and Clinical Diabetes: The TEDDY Study. Diabetes Care. 2022 Oct 1;45(10):2271-2281. doi: 10.2337/dc21-2612.
citation: Melin J, Lynch KF, Lundgren M, Aronsson CA, Larsson HE, Johnson SB; TEDDY Study Group. Is staff consistency important to parents' satisfaction in a longitudinal study of children at risk for type 1 diabetes: the TEDDY study. BMC Endocr Disord. 2022 Jan 10;22(1):19. doi: 10.1186/s12902-021-00929-w.
citation: Krischer JP, Liu X, Lernmark A, Hagopian WA, Rewers MJ, She JX, Toppari J, Ziegler AG, Akolkar B; TEDDY Study Group. Characteristics of children diagnosed with type 1 diabetes before vs after 6 years of age in the TEDDY cohort study. Diabetologia. 2021 Oct;64(10):2247-2257. doi: 10.1007/s00125-021-05514-3. Epub 2021 Jul 22.
citation: Johnson RK, Tamura R, Frank N, Uusitalo U, Yang J, Niinisto S, Andren Aronsson C, Ziegler AG, Hagopian W, Rewers M, Toppari J, Akolkar B, Krischer J, Virtanen SM, Norris JM; TEDDY Study Group. Maternal food consumption during late pregnancy and offspring risk of islet autoimmunity and type 1 diabetes. Diabetologia. 2021 Jul;64(7):1604-1612. doi: 10.1007/s00125-021-05446-y. Epub 2021 Mar 30.
citation: Frank NM, Lynch KF, Uusitalo U, Yang J, Lonnrot M, Virtanen SM, Hyoty H, Norris JM; TEDDY Study Group. The relationship between breastfeeding and reported respiratory and gastrointestinal infection rates in young children. BMC Pediatr. 2019 Sep 18;19(1):339. doi: 10.1186/s12887-019-1693-2.
citation: Hippich M, Beyerlein A, Hagopian WA, Krischer JP, Vehik K, Knoop J, Winker C, Toppari J, Lernmark A, Rewers MJ, Steck AK, She JX, Akolkar B, Robertson CC, Onengut-Gumuscu S, Rich SS, Bonifacio E, Ziegler AG; TEDDY Study Group; Teddy Study Group. Genetic Contribution to the Divergence in Type 1 Diabetes Risk Between Children From the General Population and Children From Affected Families. Diabetes. 2019 Apr;68(4):847-857. doi: 10.2337/db18-0882. Epub 2019 Jan 17.
citation: Hagopian WA, Erlich H, Lernmark A, Rewers M, Ziegler AG, Simell O, Akolkar B, Vogt R Jr, Blair A, Ilonen J, Krischer J, She J; TEDDY Study Group. The Environmental Determinants of Diabetes in the Young (TEDDY): genetic criteria and international diabetes risk screening of 421 000 infants. Pediatr Diabetes. 2011 Dec;12(8):733-43. doi: 10.1111/j.1399-5448.2011.00774.x. Epub 2011 May 12.