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Trial registered on ANZCTR


Registration number
ACTRN12625000255482
Ethics application status
Approved
Date submitted
10/02/2025
Date registered
7/04/2025
Date last updated
7/04/2025
Date data sharing statement initially provided
7/04/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Type 1 Diabetes National Screening Pilot: General Practice Feasibility and Acceptability Study
Scientific title
Childhood Type 1 Diabetes National Screening Pilot: General Practice Feasibility and Acceptability Study
Secondary ID [1] 313112 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is a sub-study of the Childhood Type 1 Diabetes National Screening Pilot: Feasibility and Acceptability Study (ACTRN12622000381785).

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 335371 0
Condition category
Condition code
Metabolic and Endocrine 331947 331947 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
BRIEF NAME & WHY:
A single-arm implementation pilot exploring the feasibility and acceptability of a type 1 diabetes screening program for the general paediatric population embedded into primary care in Australia, comprising of genetic-risk stratified screening at routine immunisations and/or health check appointments (between 6 weeks to 6 months of age) with autoantibody follow-up testing for 'increased chance children' from 12 months to 5 years of age.

WHAT (MATERIALS & PROCEDURES):
MATERIALS:
**INFORMATION MATERIALS: Parents/guardians of eligible children will be offered a study brochure upon clinic check-in. Families who express interest in participating will be provided with a hard-copy Participant Information Statement and Consent Form by their GP or Practice Nurse. Parent/guardians will also be provided with any relevant information relating to their child’s screening result (+/- follow-up result if required) e.g. explanation of the result, +/- recommendations for follow-up testing +/- specialist referral. GPs and Practice Nurses will be provided with information and training regarding T1D and study screening and follow-up pathways and procedures.

**CONSUMABLES: On-site screening sample collection kits will be provided to the GP practices for either heel prick dried bloodspots (single-use retractable lancets and Whatman 903 Proteinsaver cards) or saliva swabs (ORAcollect OC-175, DNA Genotek), depending on the protocol at the time. Follow-up dried bloodspot kits also containing single-use retractable lancets and Whatman 903 Proteinsaver cards will be provided to GP practices for on-site sampling as required (described below).


PROCEDURES
**RECRUITMENT (SCREENING) & FOLLOW-UP: Parents/guardians of children aged 6 weeks to 6 months who are attending a routine immunisation and/or health check appointment will be offered to have their child screened (polygenic risk i.e. T1D GRS2 score) using either a heel prick dried bloodspot or saliva swab,depending on the protocol at the time. Both sample collection methods are simple and quick to perform (<5 mins) and will be integrated into these routine appointments, rather than a stand-alone study appointment/visit. Recruitment (i.e. screening phase) will be open for up to 16 weeks at each site, but will cease sooner if recruitment targets are met (n=300 children in total).

- Low genetic chance children - Children identified as having a genetically ‘low chance’ of type 1 diabetes will not be offered any follow-up testing.

- Increased genetic chance children - Children identified as having a genetically ‘increased chance’ of type 1 diabetes will be offered follow-up testing for type 1 diabetes autoantibodies (finger or heel prick dried bloodspot) at 12 months of age, also during their routine immunisation/health check appointment. Positive autoantibody screens will be confirmed via a venous blood draw at a local pathology centre. Increased chance children who return a negative autoantibody test result will be offered ongoing annual follow-up autoantibody testing until they reach 5 years of age.

**POLYGENIC RISK (GRS2): Screening samples (dried bloodspot/saliva) will be analysed at Pacific Northwest Research Institute, USA. Samples will have their DNA extracted, quantitated and normalised and then genotyped using a custom type 1 diabetes and coeliac disease-specific single nucleotide polymorphism (SNP) panel (84 SNPs). Polygenic risk scores (T1D GRS2 scores) will be calculated for each sample. The polygenic risk score is a numerical summary of an individual's risk of type 1 diabetes, rather than diagnostic result. It is calculated as the weighted sum of the risk associated with 67 SNPs. Individual scores will be reported as either ‘low chance‘ or ‘increased chance’ of developing type 1 diabetes in childhood, rather than reported as numerical scores. Children with a GRS2 score of 19.09 or above will be considered to have an ‘increased chance’ of developing type 1 diabetes (risk of type 1 diabetes: 2.4% or ~1 in 40 children vs general population risk: 0.3% or 1 in 300 children). This group represents the top 10th centile of the population by type 1 diabetes risk (i.e. 1 in every 10 children will receive an ‘increased chance’ result) and captures ~80% of all future cases of type 1 diabetes diagnosed in childhood. Most children (9 in 10 children) will be below this threshold and considered to have a ‘low chance’ of developing type 1 diabetes in childhood (risk: 0.08% or 8 in 10,000 children vs general population risk: 0.3% or 1 in 300 children). Coeliac disease risk scores will not be returned to families.

**AUTOANTIBODY ANALYSIS: Follow-up dried bloodspot samples will be tested for four islet autoantibodies (insulin (IAA), glutamic acid decarboxylase (GADA), islet antigen 2 (IA-2A) and zinc transporter 8 (ZnT8A)) at Royal Melbourne Hospital using the antibody detection by agglutination-PCR (ADAP) assay for islet autoantibodies (sensitivity: 85%, specificity: 98%). Confirmation venous serum samples will be analysed in a two-step process at Royal Melbourne Hospital using the 3 Screen assay (RSR Ltd) for GADA, IA-2A and ZnT8A and individual radioimmunoassay for IAA. Where the 3 Screen is positive, confirmatory individual ELISAs for GADA, IA-2A and ZnT8A will be conducted. Samples will be concurrently analysed for HbA1c and random blood glucose at a local pathology laboratory to allow T1D staging, if detected.


WHO DELIVERED/PROVIDED THE INTERVENTION & WHERE:
The ‘intervention’ (i.e. sample collection for polygenic risk score analysis) will be performed by trained GPs or Practice Nurses during participating children's routine immunisation +/- health check appointments using on-site collection kits provided by the Pilot.
Intervention code [1] 329683 0
Early detection / Screening
Comparator / control treatment
No control group. Single arm study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339553 0
Screening uptake rate.
Timepoint [1] 339553 0
End of screening phase.
Secondary outcome [1] 440906 0
Knowledge of families (parental knowledge)
Timepoint [1] 440906 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [2] 440420 0
Reach (Penetration - children screened)
Timepoint [2] 440420 0
End of screening phase.
Secondary outcome [3] 445199 0
Acceptability for families (child quality of life)
Timepoint [3] 445199 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [4] 440422 0
Reach (Representativeness of families)
Timepoint [4] 440422 0
End of screening phase.
Secondary outcome [5] 440904 0
Acceptability for Health Professionals (satisfaction)
Timepoint [5] 440904 0
End of screening phase +/- during or end of follow-up phase, as applicable.
Secondary outcome [6] 440896 0
Reach (Primary Care adoption)
Timepoint [6] 440896 0
End of screening phase.
Secondary outcome [7] 440898 0
Feasibility for families (testing completeness)
Timepoint [7] 440898 0
End of screening phase +/- end of follow-up phase, as applicable.
Secondary outcome [8] 440897 0
Feasibility for families (barriers)
Timepoint [8] 440897 0
Pre-test (pre-screen/baseline)
Secondary outcome [9] 440421 0
Reach (Penetration - families invited)
Timepoint [9] 440421 0
End of screening phase.
Secondary outcome [10] 440901 0
Acceptability for families (parental anxiety)
Timepoint [10] 440901 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [11] 440899 0
Feasibility for Health Professionals
Timepoint [11] 440899 0
End of screening phase +/- during or end of follow-up phase, as applicable.
Secondary outcome [12] 445200 0
Acceptability for Families (parental wellbeing)
Timepoint [12] 445200 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [13] 440905 0
Acceptability for Health Professionals (attitudes)
Timepoint [13] 440905 0
End of screening phase +/- during or end of follow-up phase, as applicable.
Secondary outcome [14] 440900 0
Acceptability for families (children consented)
Timepoint [14] 440900 0
End of screening phase.
Secondary outcome [15] 440907 0
Knowledge of Health Professionals
Timepoint [15] 440907 0
End of screening phase +/- during or end of follow-up phase, as applicable.
Secondary outcome [16] 440903 0
Acceptability for families (parental attitudes)
Timepoint [16] 440903 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [17] 440908 0
Fidelity
Timepoint [17] 440908 0
End of trial.
Secondary outcome [18] 440902 0
Acceptability for families (parental satisfaction)
Timepoint [18] 440902 0
- Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [19] 445201 0
Acceptability for families (parental social support)
Timepoint [19] 445201 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)
Secondary outcome [20] 445198 0
Feasibility for families (motivators)
Timepoint [20] 445198 0
Pre-test (pre-screen/baseline)
Secondary outcome [21] 440910 0
Clinical Outcomes (exploratory)
Timepoint [21] 440910 0
End of trial.
Secondary outcome [22] 440911 0
Acceptability for families (parental quality of life)
Timepoint [22] 440911 0
- Pre-test (pre-screen/baseline) - Post-test (post-screen/upon notification of screening test result) - Post-test (post-follow-up/upon follow-up test result notification, where applicable)

Eligibility
Key inclusion criteria
Children aged 6 weeks to 6 months AND attending a routine immunisation and/or health check appointment at a recruiting general practice.
Minimum age
6 Weeks
Maximum age
6 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Pre-existing type 1 diabetes.

Study design
Purpose of the study
Diagnosis
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
All participants receive the same 'intervention' i.e. genetic stratified screening for risk of developing type 1 diabetes in childhood, however sampling methods may vary, depending on the uptake rate. That is, all GP practices will begin by offering heel prick dried bloodspot screening. If recruitment/uptake rate during weeks 3-6 is low without reason (defined by <24 children screened and/or <30% of invited families participating), we will cease heel prick sampling and switch to saliva swabs.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
As this is a single-arm, implementation-science based study, the sample size (n=300) was selected to be pragmatic and allow evaluation of the implementation strategy in practice.

Descriptive statistics will be used to assess socio-demographic characteristics, including child age, location, socio-economic status, parental age and education, country of birth, ethnicity, and family history of type 1 diabetes.

Study outcomes will be determined by scoring responses and aggregating items using appropriate scales. Frequency and proportion of responses for each study outcome of interest will be determined overall, and assessed by site and socio-demographic characteristics.

Pearson’s chi-squared, t-tests, or Wilcoxen tests will be used to compare differences between socio-demographic characteristics and study outcomes for categorical and parametric and non-parametric continuous/ ordinal variables, respectively.
Multivariate analysis will be conducted to take into account potential confounding by socio-demographic factors.

All analyses will be performed using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) and p values <0.05 considered statistically significant.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
21/04/2025
Actual
Date of last participant enrolment
Anticipated
31/08/2025
Actual
Date of last data collection
Anticipated
30/06/2031
Actual
Sample size
Target
300
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW

Funding & Sponsors
Funding source category [1] 317557 0
Charities/Societies/Foundations
Name [1] 317557 0
JDRF Australia (formerly Juvenile Diabetes Research Foundation)
Country [1] 317557 0
Australia
Funding source category [2] 318259 0
Charities/Societies/Foundations
Name [2] 318259 0
Breakthrough T1D (formerly JDRF International)
Country [2] 318259 0
United States of America
Primary sponsor type
University
Name
University of Sydney
Address
Country
Australia
Secondary sponsor category [1] 319860 0
None
Name [1] 319860 0
Address [1] 319860 0
Country [1] 319860 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316266 0
Sydney Children's Hospitals Network Human Research Ethics Committee
Ethics committee address [1] 316266 0
Ethics committee country [1] 316266 0
Australia
Date submitted for ethics approval [1] 316266 0
30/09/2024
Approval date [1] 316266 0
02/12/2024
Ethics approval number [1] 316266 0
2024/ETH02146

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

Contacts
Principal investigator
Name 137334 0
Dr Kirstine Bell
Address 137334 0
Charles Perkins Centre John Hopkins Drive Camperdown NSW 2006
Country 137334 0
Australia
Phone 137334 0
+61 286274250
Fax 137334 0
Email 137334 0
[email protected]
Contact person for public queries
Name 137335 0
Shannon Brodie
Address 137335 0
Charles Perkins Centre John Hopkins Drive Camperdown NSW 2006
Country 137335 0
Australia
Phone 137335 0
+61 1800 505 909
Fax 137335 0
Email 137335 0
[email protected]
Contact person for scientific queries
Name 137336 0
Shannon Brodie
Address 137336 0
Charles Perkins Centre John Hopkins Drive Camperdown NSW 2006
Country 137336 0
Australia
Phone 137336 0
+61 1800 505 909
Fax 137336 0
Email 137336 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No
No IPD sharing reason/comment: Individual participant data will not be made available as consent has not been obtained for this.



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.