Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12620000947909
Ethics application status
Approved
Date submitted
1/07/2020
Date registered
22/09/2020
Date last updated
23/11/2022
Date data sharing statement initially provided
22/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Using continuous glucose monitoring to detect early dysglycaemia in children participating in the Environmental Determinants of Islet Autoimmunity (ENDIA) study (Sub Protocol)
Scientific title
Using continuous glucose monitoring to detect early dysglycaemia in children participating in the ENDIA study (Sub Protocol)
Secondary ID [1] 301583 0
Nil known
Universal Trial Number (UTN)
U1111-1253-8534
Trial acronym
Linked study record
ACTRN12613000794707 - this record is a main (parent) study of this sub-study

Health condition
Health condition(s) or problem(s) studied:
Type 1 Diabetes 317956 0
Condition category
Condition code
Metabolic and Endocrine 315989 315989 0 0
Diabetes
Inflammatory and Immune System 315990 315990 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 sub-study of the main ENDIA study, which commenced recruitment in 2013 and is longitudinally following children at genetic risk of type 1 diabetes (T1D) across Australia, from pregnancy to early childhood. Therefore, this sub-study will be a longitudinal, prospective study of early dysglycemia in young children at genetic risk of T1D currently enrolled in the main ENDIA study. Participants between 1 to 10 years of age will wear a continuous glucose monitoring (CGM) device continuously for a minimum of 14 days, every 6 months, or sooner, if they are autoantibody positive.

The aims of this sub-study are to characterise early dysglycemia using 2 weeks of blinded CGM and analyse CGM measures of glycemic variability in current ENDIA participants with, and without, persistent islet autoantibodies. CGM will be inserted by trained study staff onto the upper buttock of the participant via an autoinjector. Participant and caregiver will be blinded to the real-time readings from the CGM (i.e. no intervention for any high or low readings). Persistent is defined as measured on 2 or more blood tests taken at least 3 months apart; and multiple is defined as 2 or more islet autoantibodies (IAA, IA2A, GADA or ZnT8) in the main ENDIA study.
Intervention code [1] 317878 0
Early Detection / Screening
Comparator / control treatment
Age and sex matched participants with no detectable islet autoantibodies will wear a continuous glucose monitoring (CGM) device under the same conditions as the group with islet autoantibodies.
Control group
Active

Outcomes
Primary outcome [1] 324192 0
Glycemic variability: Glycemic variability is a description of the amplitude, frequency, and duration of fluctuations in glucose measurements that contribute to dysglycemia, and can reflect impairment of glucose homeostasis. Glycemic variability will be measured using various CGM metrics including, sensor glucose standard deviation, coefficient of variation, maximum daytime/nighttime glucose and mean amplitude of glycaemic excursions (MAGE).
Timepoint [1] 324192 0
Measured continuously every 5 minutes across 2 weeks from the start of blinded CGM wear.
Secondary outcome [1] 383978 0
% Time that blood glucose levels are > 7.8 mmol/L (140 mg/dL), as measured from blinded CGM
Timepoint [1] 383978 0
Measured continuously every 5 minutes across 2 weeks from the start of blinded CGM wear.
Secondary outcome [2] 416120 0
% Time spent in range 3.9 - 7.8 mmol/L (70 - 140 mg/dL) - calculated from blinded CGM sensor glucose measurements
Timepoint [2] 416120 0
Measured continuously every 5 minutes across 2 weeks from start of blinded CGM wear.

Eligibility
Key inclusion criteria
Main ENDIA study participants with persistent islet autoantibodies will be eligible to participate in this research. Age and sex matched ENDIA participants with no islet autoantibodies will also be invited to participate in this sub-study.
Minimum age
12 Months
Maximum age
10 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Incapacity for the parents to understand the requirements of their and their child’s participation. This may be due to illiteracy, cognitive impairment, an intellectual disability or mental illness.

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
T-tests will be used to compare normally distributed measures, including the primary outcome. Where outcomes are non-normally distributed, Mann-Whitney-Wilcoxon U tests will be used to compare groups. To analyse counts of events, Poisson or negative binomial regression (in the case of overdispersion) will be used.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
5/10/2020
Actual
15/10/2020
Date of last participant enrolment
Anticipated
15/09/2024
Actual
Date of last data collection
Anticipated
30/09/2024
Actual
Sample size
Target
70
Accrual to date
54
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC
Recruitment hospital [1] 16946 0
Perth Children's Hospital - Nedlands
Recruitment hospital [2] 16947 0
Barwon Health - Geelong Hospital campus - Geelong
Recruitment hospital [3] 16948 0
Monash Medical Centre - Clayton campus - Clayton
Recruitment hospital [4] 16949 0
Womens and Childrens Hospital - North Adelaide
Recruitment hospital [5] 16950 0
St George Hospital - Kogarah
Recruitment hospital [6] 16951 0
Royal Hospital for Women - Randwick
Recruitment hospital [7] 16952 0
The Children's Hospital at Westmead - Westmead
Recruitment hospital [8] 16954 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [9] 16987 0
Queensland Children's Hospital - South Brisbane
Recruitment postcode(s) [1] 30603 0
6009 - Nedlands
Recruitment postcode(s) [2] 30604 0
3220 - Geelong
Recruitment postcode(s) [3] 30605 0
3168 - Clayton
Recruitment postcode(s) [4] 30606 0
5006 - North Adelaide
Recruitment postcode(s) [5] 30607 0
2217 - Kogarah
Recruitment postcode(s) [6] 30608 0
2031 - Randwick
Recruitment postcode(s) [7] 30609 0
2145 - Westmead
Recruitment postcode(s) [8] 30611 0
3050 - Parkville
Recruitment postcode(s) [9] 30649 0
4101 - South Brisbane

Funding & Sponsors
Funding source category [1] 306010 0
Charities/Societies/Foundations
Name [1] 306010 0
Diabetes Research WA
Country [1] 306010 0
Australia
Funding source category [2] 306011 0
Charities/Societies/Foundations
Name [2] 306011 0
Australasian Paediatric Endocrine Group
Country [2] 306011 0
Australia
Funding source category [3] 306012 0
Charities/Societies/Foundations
Name [3] 306012 0
Women's and Children's Hospital Foundation
Country [3] 306012 0
Australia
Funding source category [4] 312723 0
Charities/Societies/Foundations
Name [4] 312723 0
The Leona M. and Harry B. Helmsley Foundation
Country [4] 312723 0
United States of America
Funding source category [5] 312724 0
Charities/Societies/Foundations
Name [5] 312724 0
Juvenile Diabetes Research Foundation
Country [5] 312724 0
United States of America
Funding source category [6] 312725 0
Charities/Societies/Foundations
Name [6] 312725 0
Raine Medical Research Foundation
Country [6] 312725 0
Australia
Primary sponsor type
Charities/Societies/Foundations
Name
Telethon Kids Institute
Address
Perth Children's Hospital
15 Hospital Avenue
Nedlands WA 6009
Country
Australia
Secondary sponsor category [1] 306473 0
University
Name [1] 306473 0
University of Adelaide
Address [1] 306473 0
Adelaide SA 5005
Country [1] 306473 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306245 0
Child and Adolescent Health Service Human Research Ethics Committee
Ethics committee address [1] 306245 0
Perth Children's Hospital
15 Hospital Avenue
Nedlands WA 6009
Ethics committee country [1] 306245 0
Australia
Date submitted for ethics approval [1] 306245 0
18/02/2019
Approval date [1] 306245 0
08/04/2019
Ethics approval number [1] 306245 0
RGS0000002402
Ethics committee name [2] 306246 0
Women's and Children's Health Network Human Research Ethics Committee
Ethics committee address [2] 306246 0
Level 2, Samuel Way Building
72 King William Road
North Adelaide SA 5006
Ethics committee country [2] 306246 0
Australia
Date submitted for ethics approval [2] 306246 0
16/01/2020
Approval date [2] 306246 0
29/01/2020
Ethics approval number [2] 306246 0
HREC/16/WCHN/66

Summary
Brief summary
Type 1 diabetes (T1D) is classically regarded as a metabolic disorder diagnosed when the symptoms of persistently high blood glucose levels appear. The clinical presentation, however, follows an extended period of months to years when the immune system attacks the insulin producing cells in the pancreas. Prospective longitudinal studies of older children at genetic risk of T1D have shown that impaired glucose homeostasis starts much earlier than symptomatic diabetes. A gradual decline in insulin secretion and beta cell sensitivity can be detected at least 2 years before the onset of clinical symptoms, and these changes become more rapid in the last few months prior to diagnosis. Higher glucose levels and increased glycaemic variability are also detectable prior to the onset of clinical T1D. This recent recognition that T1D progresses in these three distinct stages has led to a paradigm shift that re-defines T1D as an autoimmune beta cell disorder with clear characteristics associated with Stage 1, Stage 2, and Stage 3 (symptomatic) disease. The purpose of this sub-study is to undertake serial measurements of continuous glucose monitoring data in the ENDIA protocol that will provide the longitudinal data required to define the transition in islet autoantibody-positive children from normoglycaemia (Stage 1 T1D) to dysglycaemia (Stage 2 T1D). Moreover, it will enable characterisation of asymptomatic hyper- or hypo-glycaemia and inform clinical care for such children prior to onset of symptomatic clinical T1D (State 3 T1D).
Trial website
http://www.endia.org.au
Trial related presentations / publications
Public notes
Initial approval to conduct the sub-study was submitted as an amendment to the main ENDIA project.

Contacts
Principal investigator
Name 103226 0
Prof Jennifer Couper
Address 103226 0
Women and Children's Hospital Adelaide
72 King William Road
North Adelaide
South Australia 5006
Country 103226 0
Australia
Phone 103226 0
+61 8 8161 6402
Fax 103226 0
Email 103226 0
[email protected]
Contact person for public queries
Name 103227 0
Dr Aveni Haynes
Address 103227 0
Telethon Kids Institute
Perth Children's Hospital
Northern Entrance
15 Hospital Avenue
Nedlands WA 6009
Country 103227 0
Australia
Phone 103227 0
+61 8 6465 4647
Fax 103227 0
Email 103227 0
[email protected]
Contact person for scientific queries
Name 103228 0
Dr Aveni Haynes
Address 103228 0
Telethon Kids Institute
Perth Children's Hospital
Northern Entrance
15 Hospital Avenue
Nedlands WA 6009
Country 103228 0
Australia
Phone 103228 0
+61 8 6465 4647
Fax 103228 0
Email 103228 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
CGM traces and logbook data will be available. 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: 1/11/2024 or following publication of the study findings
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. 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?
Contact Principal Investigator of the study, Dr Aveni Haynes via email [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
8284Study protocol  [email protected]
8285Ethical approval  [email protected] 380042-(Uploaded-19-06-2020-18-43-24)-Study-related document.pdf
8628Ethical approval  [email protected] 380042-(Uploaded-28-07-2020-16-42-28)-Study-related document.pdf



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.