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Trial registered on ANZCTR


Registration number
ACTRN12625000026426
Ethics application status
Approved
Date submitted
5/12/2024
Date registered
15/01/2025
Date last updated
15/01/2025
Date data sharing statement initially provided
15/01/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Monitoring glucose levels in Australian children with early stage type 1 diabetes (T1D)
Scientific title
TRends in continuous glucose monitoring measures of glycaemic variability in Australian Children with Early stage T1D (TRACE-T1D study)
Secondary ID [1] 312825 0
Nil known
Universal Trial Number (UTN)
Trial acronym
TRACE-T1D
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 334934 0
Condition category
Condition code
Metabolic and Endocrine 331472 331472 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Consenting visit
During this appointment, the parent/ guardian or mature minor will have a one-on-one telehealth appointment with a study team member who has expertise in CGM. Study procedures will be explained to ensure informed consent is received. Consent will be obtained via an online link. Demographics will be collected, and the parent/ guardian or mature minor will be emailed a video link that demonstrates sensors insertion, pairing and removal of the sensor (two 2-minute videos).

CGM session
A Researcher will liaise via phone or email to arrange the best time to commence a session.
NOTE: For participants having glycaemic tests (e.g.HbA1c, random glucose or OGTT) as part of their clinical care, they can choose to wear CGM to coincide with when these measures are being conducted to enable these measures to be correlated with their CGM-derived metrics.
The CGM system that will be utilised in this study will be the Dexcom G7, The Dexcom G7 sensors are factory-calibrated and do not require wearers to undergo finger prick blood glucose testing for calibration, enabling accurate sensor glucose readings to be conducted with minimal burden to participants.
Equipment will be posted to an address chosen by the participant in a tracked postage satchel. The majority of participants will have a 1st degree relative with type 1 diabetes and hence have some experience with CGM insertion. For families who are not confident in sensor insertion phone support will be offered at a time suitable to both. Following 10-days of sensor wear, parent/ guardian or the mature minor will be advised to remove the first sensor and insert a second sensor to continue the CGM wear period. If the sensor falls off prior to 10 days, the parent/guardian or mature minor can reinsert a second sensor immediately.
With every sensor that is removed the parent/guardian or mature minor will be asked to inspect the skin to ensure its integrity. This information will be recorded on paper or electronically as per the preference of the parent/guardian or mature minor. If after wearing the second sensor the participant has worn it for <14 days they will have a third sensor that can be inserted.
A maximum of 3 sensors will be provided for each session to obtain a minimum of 14 days data.
Whilst wearing the CGM, participants are encouraged continue their usual activities and eating habits. Researchers will liaise with the parent/ guardian or mature minor via phone and email during the study period and be available by a dedicated study phone number for troubleshooting or questions during usual working hours.
At completion of the session the parent/ guardian or mature minor will be provided with a paid postage satchel to return all the equipment to the co-ordinating study site.

This study protocol includes 6-monthly CGM for participants with no evidence of dysglycaemia (Stage 1) and 3-monthly CGM for participants with evidence of dysglycaemia from either traditional measures of glycaemia or CGM data.

CGM data upload
Following a session when the equipment is received back at co-ordinating study site the CGM data will be uploaded to a secure-access study specific CLARITY® clinic database that is cloud-based. The receiver will store data for 90 days ensuring plenty of time for the parent/ guardian or mature minor to return the equipment. The information uploaded into CLARITY® is TLS encrypted using TLS 1.1 or higher and will not contain any personal information with participants labelled by a unique study identifier.
The researcher will notify the principal study investigator and clinical investigator/referring clinician that the participant has completed a CGM session and that CGM data have been uploaded to the study-specific CLARITY® clinic database. A PDF will be emailed to the referring clinician of the CLARITY® generated reports (Daily CGM traces, summary Ambulatory Glucose Profile (AGP) as part of this notification. These reports will provide details on the participants’ glucose values during the CGM wear period and enable the referring clinician to provide appropriate feedback to the participant and their family.
Feedback from the session will be given to the parent/guardian or mature minor by the clinical investigator/referring clinician. This will include being provided with a paper/electronic copy of the AGP and recommendations on clinical follow-up.

Survey
All parents/guardians will be asked to complete a survey each year to gather information on parents’ experiences related to the application and use of the CGM, and any worry or anxiety caused by using the device or the information they receive.
Additionally, an age-appropriate survey will also be offered to all children aged 8 years of age and above to answer questions related to their overall experiences.
Survey questions will include those requiring answers using a Likert scale, short answers and multiple-choice answers.

Participants will reach study completion when they are diagnosed with clinical type 1
diabetes and commence treatment with insulin (Stage 3), turn 18 years old, or the study
ends, currently scheduled for end 2030.
Intervention code [1] 329387 0
Early detection / Screening
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 339233 0
Change in glycaemic variability
Timepoint [1] 339233 0
Following each CGM session
Primary outcome [2] 340137 0
Change in glycaemic variability
Timepoint [2] 340137 0
Following each session
Secondary outcome [1] 439182 0
HbA1c
Timepoint [1] 439182 0
Baseline, following each session and/or 6-monthly until study end in 2030.
Secondary outcome [2] 442922 0
Acceptability
Timepoint [2] 442922 0
yearly until study end in 2030.
Secondary outcome [3] 442925 0
Psychosocial impact
Timepoint [3] 442925 0
yearly until study end in 2030.
Secondary outcome [4] 443508 0
random plasma glucose
Timepoint [4] 443508 0
Baseline, following each session and/or 6-monthly until study end in 2030.
Secondary outcome [5] 443509 0
oral glucose test (OGTT) measurements on fasting glucose
Timepoint [5] 443509 0
Baseline, following each session and/or 6-monthly until study end in 2030.
Secondary outcome [6] 443510 0
c-peptide
Timepoint [6] 443510 0
Baseline, following each session and/or 6-monthly until study end in 2030.

Eligibility
Key inclusion criteria
The inclusion criteria for this study are children or adolescents aged between 2 and 18 years old, living in Australia who have one or more detectable islet autoantibodies (IAA, IA2A, GADA, ZnT8A), and are being managed by a clinician or paediatric endocrinologist for their clinical care.
Children, adolescents and their parents/guardians must be able to understand and willingly provide written informed consent to participate in the study.
Minimum age
2 Years
Maximum age
18 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
The only exclusion criterion for the study is the incapacity for the parents/guardians to understand the requirements of the study and the participation for themselves and their child. This may be due to illiteracy, cognitive impairment, an intellectual disability or a mental illness. If a cognitive impairment, intellectual disability or mental illness is reported or suspected, investigators will liaise with the referring clinician to undertake a clinical assessment to determine the participant's capacity to be able to decide whether to take part.

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
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis
To address primary aims:
Describing glycaemic variability
Mean and SD of sensor glucose values will be calculated using all available readings collected within each CGM wear period. CEV will be calculated as SD sgl/mean sgl. Percent time in ranges will be calculated by dividing the number of observations in that range by the total number of observations and multiplying by 100.
The mean (SD)/median (IQR) will be presented at baseline for all CGM-derived metrics for the entire sample and by demographic and clinical factors of interest (sex assigned at birth, age at time of islet autoantibody detection, duration of islet autoimmunity, HLA haplotype (DR34 vs other).

Prediction of progression to clinical type 1 diabetes
Kaplan Meier survival curves plotting the time to clinical diagnosis of type 1 diabetes will be produced for the overall sample and stratified by baseline factors of interest (sex assigned at birth, age at time of islet autoantibody detection, HLA haplotype (DR34 vs other)). A Cox proportional hazards model will be conducted to estimate the hazard ratio associated with the primary predictor of interest (e.g., =10% time spent > 7.8 mmol/L at baseline) whilst adjusting for appropriate baseline characteristics. An extended Cox model will be conducted to estimate the hazard ratio associated with the time varying predictor (=10% time spend > 7.8 mmol/L collected every 6 months).

Longitudinal trends in glycaemic variability
Scatterplots and spaghetti plots will be constructed displaying each glycaemic outcome against time.
A linear mixed model examining SD sgl with a fixed effects term for time and including a random intercept and slope will be conducted to identify the linear trend in SD sgl over time and the variability around the trend. A similar approach will be employed to examine % Time >7.8 mmol/L.
Further exploratory models including both time invariant and time-varying factors and their interaction with time will be conducted to identify characteristics/events associated with the trend in glycaemic control.
Residuals will be inspected for normality and homoscedasticity. If departures are noted, logarithmic transformation will be applied prior to modelling. If transformation is not successful, alternative methods will be explored (e.g., gamma generalised linear mixed effects model, Box-Cox transformation). Sensitivity models will be conducted to explore how drop-out due to T1D diagnosis may influence the parameters of the model.

Joint modelling
A joint modelling approach will also be investigated to explore the trends in glycaemic control (SD sgl) over time; this will allow for estimates that account for the informative censoring of participants following a confirmed T1D diagnosis. It will also allow for exploration of the association between the longitudinal measurements and risk of progression. The joint model will consist of a longitudinal submodel for SD sgl and a submodel for T1D progression risk.
The list of characteristics that will be explored as factors in the models described above will be:
• Age at seroconversion
• Sex
• HLA type (3/4 y/n)
• Antibody type

To address secondary aims:
Correlation with traditional measures of glycaemia
The association between each of the CGM-derived metrics and traditional diagnostic measures will be explored using repeated measures correlation coefficient.

Survey data
Survey data will be analysed using content analysis to gain insight into responses and concepts from individuals experience.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
7/02/2025
Actual
Date of last participant enrolment
Anticipated
27/09/2030
Actual
Date of last data collection
Anticipated
14/10/2030
Actual
Sample size
Target
120
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,WA,VIC
Recruitment hospital [1] 27026 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 27027 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 27028 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [4] 27029 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [5] 27030 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [6] 27031 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 43096 0
6009 - Nedlands
Recruitment postcode(s) [2] 43097 0
3050 - Parkville
Recruitment postcode(s) [3] 43098 0
5006 - North Adelaide
Recruitment postcode(s) [4] 43099 0
2145 - Westmead
Recruitment postcode(s) [5] 43100 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 317263 0
Charities/Societies/Foundations
Name [1] 317263 0
Breakthrough T1D
Country [1] 317263 0
United States of America
Primary sponsor type
Other
Name
The Kids Research Institute Australia
Address
Country
Australia
Secondary sponsor category [1] 320329 0
None
Name [1] 320329 0
Address [1] 320329 0
Country [1] 320329 0
Other collaborator category [1] 283150 0
University
Name [1] 283150 0
University of Western Australia
Address [1] 283150 0
Country [1] 283150 0
Australia
Other collaborator category [2] 283151 0
Hospital
Name [2] 283151 0
Perth Children's Hospital
Address [2] 283151 0
Country [2] 283151 0
Australia
Other collaborator category [3] 283152 0
Hospital
Name [3] 283152 0
Royal Melbourne Hospital
Address [3] 283152 0
Country [3] 283152 0
Australia
Other collaborator category [4] 283153 0
Other
Name [4] 283153 0
Walter and Eliza Hall Institute
Address [4] 283153 0
Country [4] 283153 0
Australia
Other collaborator category [5] 283154 0
University
Name [5] 283154 0
University of Adelaide
Address [5] 283154 0
Country [5] 283154 0
Australia
Other collaborator category [6] 283155 0
Hospital
Name [6] 283155 0
Women's and Children's Hospital, South Australia
Address [6] 283155 0
Country [6] 283155 0
Australia
Other collaborator category [7] 283156 0
Hospital
Name [7] 283156 0
Children's Health Queensland Hospital and Health Service
Address [7] 283156 0
Country [7] 283156 0
Australia
Other collaborator category [8] 283157 0
Hospital
Name [8] 283157 0
Royal Children's Hospital
Address [8] 283157 0
Country [8] 283157 0
Australia
Other collaborator category [9] 283158 0
University
Name [9] 283158 0
University of New South Wales
Address [9] 283158 0
Country [9] 283158 0
Australia
Other collaborator category [10] 283159 0
Hospital
Name [10] 283159 0
Children's Hospital at Westmead
Address [10] 283159 0
Country [10] 283159 0
Australia
Other collaborator category [11] 283160 0
University
Name [11] 283160 0
Macquarie University
Address [11] 283160 0
Country [11] 283160 0
Australia
Other collaborator category [12] 283161 0
University
Name [12] 283161 0
Monash University
Address [12] 283161 0
Country [12] 283161 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 316003 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 316003 0
https://cahs.health.wa.gov.au/Research/For-researchers/Ethics-and-governance-approval
Ethics committee country [1] 316003 0
Australia
Date submitted for ethics approval [1] 316003 0
26/08/2024
Approval date [1] 316003 0
12/09/2024
Ethics approval number [1] 316003 0

Summary
Brief summary
In this study, we want to learn about how and when glucose levels measured using continuous glucose monitoring (CGM) in Australian children change over time so that we can better understand how T1D develops. By monitoring changes in glucose levels and patterns with CGM, this study will also provide useful additional information on whether these children are progressing towards a clinical diagnosis of T1D, and treatment with insulin. The CGM will be worn “blinded” meaning no glucose readings will be visible to participants whilst wearing the CGM. Participants will be asked to wear at least 2 sensors, each lasting up-to 10 days to obtain at least 14 days of glucose data. These CGM sensors will be worn at a minimum every 6 months until either the participant no longer wishes to participate, turns 18 years old, develops clinical T1D or the study finishes. This study hypothesises that CGM can be used as a tool in children with islet autoantibodies to identify those who are more likely to progress or closer to clinical diagnosis and prevent the likelihood to DKA at diagnosis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 136466 0
Dr Aveni Haynes
Address 136466 0
The Kids Research Institute Australia, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA, 6009
Country 136466 0
Australia
Phone 136466 0
+61 8 6456 4647
Fax 136466 0
Email 136466 0
[email protected]
Contact person for public queries
Name 136467 0
Aveni Haynes
Address 136467 0
The Kids Research Institute Australia, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA, 6009
Country 136467 0
Australia
Phone 136467 0
+61 8 6456 4647
Fax 136467 0
Email 136467 0
[email protected]
Contact person for scientific queries
Name 136468 0
Aveni Haynes
Address 136468 0
The Kids Research Institute Australia, Perth Children's Hospital, 15 Hospital Avenue, Nedlands, WA, 6009
Country 136468 0
Australia
Phone 136468 0
+61 8 6456 4647
Fax 136468 0
Email 136468 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only aggregate data will be published. Individual data will only go to the participant's treating doctor


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.