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Trial registered on ANZCTR


Registration number
ACTRN12613000794707
Ethics application status
Approved
Date submitted
12/07/2013
Date registered
16/07/2013
Date last updated
23/01/2020
Date data sharing statement initially provided
29/01/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Why are more children getting Type 1 Diabetes? Exploring the environmental triggers islet autoimmunity and type 1 diabetes
Scientific title
In children with a first-degree relative with type 1 diabetes, do prenatal and postnatal environmental factors contribute to the development of islet autoimmunity and type 1 diabetes
Secondary ID [1] 282812 0
Nil known
Universal Trial Number (UTN)
Nil
Trial acronym
ENDIA
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 289587 0
Condition category
Condition code
Metabolic and Endocrine 289923 289923 0 0
Diabetes
Inflammatory and Immune System 289924 289924 0 0
Autoimmune diseases

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
This is a pregnancy/birth cohort study of children with a first-degree relative with type 1 diabetes. Pregnant mothers and their infants will be followed prospectively from early pregnancy through childhood to investigate relationships between the development of islet autoimmunity (and subsequently type 1 diabetes) and prenatal and postnatal environmental factors. Investigation will involve 3-monthly assessments of the mother during pregnancy, then 3-monthly assessments of the child until 24 months of age and 6-monthly thereafter.

The initial duration of the study is until the child reaches three years of age. We would like to continue to follow these children longer-term into adolescence to determine the relationship between genotype and early environment and the development of islet autoimmunity and type 1 diabetes. Participants will be asked to sign a separate consent form to follow their children from three to ten years of age.
Intervention code [1] 287496 0
Not applicable
Comparator / control treatment
Not applicable
Control group
Uncontrolled

Outcomes
Primary outcome [1] 289981 0
Development of antibodies against one or more of the following islet autoantigens detected in serum: glutamic acid decarboxylase 65 (GAD) tyrosine phosphatase-like insulinoma antigen (IA2), insulin, and beta cell-specific zinc transporter 8 (ZnT8).

Insulin autoantibodies will be measured by fluid phase radiobinding assay. ZnT8 autoantibodies will be measured by precipitation of 35S-methionine labelled recombinant human ZnT8 protein. GAD and IA2 autoantibodies will be measured by ELISA.
Timepoint [1] 289981 0
Islet autoantibodies will be measured 3-monthly from birth until 24 months of age and 6-monthly thereafter up to 3 years of age in the first instance and 10 years of age in the second instance.
Secondary outcome [1] 303702 0
Development of type 1 diabetes as measured by blood glucose testing and HbA1c analysis.
Timepoint [1] 303702 0
Assessed on a 3-6 monthly basis after the detection of islet autoantibodies up to 3 years of age in the first instance and 10 years of age in the second instance.

Eligibility
Key inclusion criteria
An unborn child with a first-degree relative with type 1 diabetes, targeting the mother for recruitment during pregnancy from six weeks gestation onwards, or an infant less than six months of age with a first-degree relative with type 1 diabetes. A first-degree relative may be the child's mother, father or sibling.
Minimum age
No limit
Maximum age
6 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Incapacity for the pregnant woman, or in the case of postnatal recruitment the child’s primary caregiver, to understand the requirements of her and/or her child’s participation in the study.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Convenience sample
Timing
Prospective
Statistical methods / analysis
1500 participants will be followed throughout Australia for a median of two years with a 9% rate of persistent islet autoimmunity. Maximum total dropout/lost to follow-up rate is estimated at 15% with the majority of dropouts occurring in the first six months of follow-up. 1200 of the 1500 total study population will be recruited in pregnancy.

For prenatal exposures from 1200 participants, using nQuery Advisor, with 600 participants above the median and 600 below, for a given exposure variable the power is 90% to detect a difference between a survival (i.e. no islet autoimmunity) of 93% in one group and a survival of 88% in the other – with 108 events (islet autoimmunity) or 9% of the total sample of 1200. For examining interactions between uncorrelated exposure variables with approximately 375 participants per combination of above/below the median, the power is 77% to detect a difference in survival (no islet autoimmunity) between 93% and 87% (70 events in 600 participants required).

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
15/02/2013
Actual
15/02/2013
Date of last participant enrolment
Anticipated
31/12/2019
Actual
4/12/2019
Date of last data collection
Anticipated
1/09/2030
Actual
Sample size
Target
1500
Accrual to date
Final
1510
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 1266 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [2] 1268 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 1270 0
Mater Mother's Hospital - South Brisbane
Recruitment hospital [4] 1271 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [5] 1273 0
Royal Hospital for Women - Randwick
Recruitment hospital [6] 1274 0
St George Hospital - Kogarah
Recruitment hospital [7] 10121 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [8] 10122 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [9] 14211 0
Perth Children's Hospital - Nedlands
Recruitment postcode(s) [1] 7154 0
5006 - North Adelaide
Recruitment postcode(s) [2] 7156 0
4101 - South Brisbane
Recruitment postcode(s) [3] 7157 0
2145 - Westmead
Recruitment postcode(s) [4] 7158 0
2031 - Randwick
Recruitment postcode(s) [5] 7159 0
2217 - Kogarah
Recruitment postcode(s) [6] 21656 0
3168 - Clayton
Recruitment postcode(s) [7] 21657 0
3220 - Geelong
Recruitment postcode(s) [8] 27193 0
6009 - Nedlands

Funding & Sponsors
Funding source category [1] 287594 0
Government body
Name [1] 287594 0
National Health and Medical Research Council
Country [1] 287594 0
Australia
Funding source category [2] 298784 0
Charities/Societies/Foundations
Name [2] 298784 0
JDRF Australia
Country [2] 298784 0
Australia
Funding source category [3] 298785 0
Charities/Societies/Foundations
Name [3] 298785 0
JDRF International
Country [3] 298785 0
United States of America
Funding source category [4] 298786 0
Charities/Societies/Foundations
Name [4] 298786 0
The Leona M. and Harry B. Helmsley Charitable Trust
Country [4] 298786 0
United States of America
Primary sponsor type
University
Name
University of Adelaide
Address
Adelaide, SA 5005
Country
Australia
Secondary sponsor category [1] 286340 0
University
Name [1] 286340 0
University of New South Wales
Address [1] 286340 0
High St, Kensington, NSW 2052
Country [1] 286340 0
Australia
Secondary sponsor category [2] 286341 0
Hospital
Name [2] 286341 0
Melbourne Health
Address [2] 286341 0
The Royal Melbourne Hospital, Parkville, Vic 3050
Country [2] 286341 0
Australia
Secondary sponsor category [3] 286342 0
University
Name [3] 286342 0
University of Western Australia
Address [3] 286342 0
35 Stirling Highway, Crawley, WA 6009
Country [3] 286342 0
Australia
Secondary sponsor category [4] 286343 0
Hospital
Name [4] 286343 0
Mater Health Service
Address [4] 286343 0
Raymond Terrace, South Brisbane, QLD 4101
Country [4] 286343 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 289565 0
Women's and Children's Health Network HREC
Ethics committee address [1] 289565 0
Ethics committee country [1] 289565 0
Australia
Date submitted for ethics approval [1] 289565 0
Approval date [1] 289565 0
10/04/2012
Ethics approval number [1] 289565 0
REC2456 & HREC/16/WCHN/66
Ethics committee name [2] 289566 0
Princess Margaret Hospital for Children HREC
Ethics committee address [2] 289566 0
Ethics committee country [2] 289566 0
Australia
Date submitted for ethics approval [2] 289566 0
Approval date [2] 289566 0
02/07/2012
Ethics approval number [2] 289566 0
1989/EP
Ethics committee name [3] 289567 0
Sydney Children’s Hospital Network HREC
Ethics committee address [3] 289567 0
Ethics committee country [3] 289567 0
Australia
Date submitted for ethics approval [3] 289567 0
Approval date [3] 289567 0
12/03/2013
Ethics approval number [3] 289567 0
12/SCHN/296
Ethics committee name [4] 289568 0
St John of God Health Care HREC
Ethics committee address [4] 289568 0
Ethics committee country [4] 289568 0
Australia
Date submitted for ethics approval [4] 289568 0
Approval date [4] 289568 0
13/02/2013
Ethics approval number [4] 289568 0
592
Ethics committee name [5] 289569 0
Mater Health Services HREC
Ethics committee address [5] 289569 0
Ethics committee country [5] 289569 0
Australia
Date submitted for ethics approval [5] 289569 0
Approval date [5] 289569 0
21/02/2013
Ethics approval number [5] 289569 0
1941C
Ethics committee name [6] 289570 0
Melbourne Health HREC
Ethics committee address [6] 289570 0
Ethics committee country [6] 289570 0
Australia
Date submitted for ethics approval [6] 289570 0
Approval date [6] 289570 0
11/04/2013
Ethics approval number [6] 289570 0
2012.147

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41350 0
Prof Jennifer Couper
Address 41350 0
Endocrinology and Diabetes Department
Level 2, Clarence Rieger Building
Women's and Children's Hospital
72 King William Road
North Adelaide, 5006
South Australia
Country 41350 0
Australia
Phone 41350 0
+61 8 81616242
Fax 41350 0
Email 41350 0
jennifer.couper@adelaide.edu.au
Contact person for public queries
Name 41351 0
Megan Penno
Address 41351 0
University Department of Paediatrics
Level 2, Clarence Rieger Building
Women's and Children's Hospital
72 King William Road
North Adelaide, 5006
South Australia
Country 41351 0
Australia
Phone 41351 0
+61 8 81618747
Fax 41351 0
Email 41351 0
megan.penno@adelaide.edu.au
Contact person for scientific queries
Name 41352 0
Len Harrison
Address 41352 0
Diabetes Laboratory, Molecular Medicine Division
Walter and Eliza Hall Institute of Medical Research
1G Royal Parade
Parkville, 3052
Victoria
Country 41352 0
Australia
Phone 41352 0
+61 3 93452461
Fax 41352 0
Email 41352 0
harrison@wehi.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Information pertaining to health, lifestyle and environment, and nutrition.
Biological samples including DNA, blood, stool, urine, swabs, placenta tissue, cord tissues, breastmilk, deciduous teeth. In any data sharing arrangement the privacy of the participants will be protected by de-identification and removal of potentially sensitive data elements as required by the HREC.
When will data be available (start and end dates)?
Start date: 1/1/2018
End date: 1/6/2045 (expected date that the youngest participant will turn 25 years old)
Available to whom?
Any individual, group or institution may submit a request to access de-identified data and/or biospecimens . In making its resources available to internal or external collaborators, the ENDIA Study Team is bound by its obligations to the Study participants, Human Research Ethics Committees, National Statement of Ethical Conduct in Human Research, institutions, government agencies, key stakeholders.
Available for what types of analyses?
Analyses may or may not be directly associated with type 1 diabetes.
How or where can data be obtained?
The defined mechanism for applying for access to ENDIA samples and/or data using the ENDIA Sample/Data Access Concept (ESDAC) system is outlined on the ENDIA website (www.endia.org.au). Biological samples will be provided directly from the central repository in Adelaide. Data will be provided electronically.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
1156Study protocol    https://bmcpediatr.biomedcentral.com/articles/10.1... [More Details]



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseType 1 diabetes: a disease of developmental origins.2017https://dx.doi.org/10.1111/pedi.12425
EmbaseDistinct gut virome profile of pregnant women with type 1 diabetes in the ENDIA study.2019https://dx.doi.org/10.1093/ofid/ofz025
EmbaseA surge in serum mucosal cytokines associated with seroconversion in children at risk for type 1 diabetes.2023https://dx.doi.org/10.1111/jdi.14031
N.B. These documents automatically identified may not have been verified by the study sponsor.