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Trial registered on ANZCTR


Registration number
ACTRN12620000190909
Ethics application status
Approved
Date submitted
31/01/2020
Date registered
19/02/2020
Date last updated
4/04/2024
Date data sharing statement initially provided
19/02/2020
Date results information initially provided
4/04/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
A comparison of FreeStyle Libre 2 to self-monitoring of blood glucose in children with type 1 diabetes and sub-optimal glycaemic control: The FLASH-2 Study
Scientific title
A comparison of FreeStyle Libre 2 to self-monitoring of blood glucose in children with type 1 diabetes and sub-optimal glycaemic control: The FLASH-2 Study
Secondary ID [1] 299857 0
ADHB A+ Number 8211
Universal Trial Number (UTN)
U1111-1237-0090
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 315259 0
Condition category
Condition code
Metabolic and Endocrine 313559 313559 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Flash glucose monitoring provides accurate and up-to-date glucose data and can be used as a replacement for finger-prick blood glucose monitoring. The flash glucose monitoring system consists of an interstitial glucose sensor worn in the upper arm continuously for up to 14 days, which is scanned by a hand-held reader to display glucose data. Glucose data includes the current glucose level, predicted glucose trend, and a graph of glucose levels from the previous 8 hours. At the baseline study visits, participants randomized to the intervention group will receive a 12-week supply of sensors (6 sensors) and approximately 30 minutes of face-to-face education by trained staff (a research nurse with diabetes knowledge) based on the manufacturer's users guide on how to apply sensors and interpret glucose data for informing treatment decisions. Participants will be instructed to scan a minimum of 10 times each day and parents will be instructed to scan at least one time per night (after 9 PM). Adherence to scanning recommendations will be monitored from data downloaded from the flash glucose monitoring system.
14 days from the start of flash glucose monitoring (the day the first sensor change is due) participants or a parent/guardian will apply the new sensor under the supervision of trained staff and apply all sensors on their own for the remainder of the study. Participants in this group will also receive an additional 30 minutes of education on scanning, trends, and hypoglycaemia treatment.
Intervention code [1] 316115 0
Treatment: Devices
Intervention code [2] 316116 0
Behaviour
Intervention code [3] 316117 0
Lifestyle
Comparator / control treatment
Participants randomized to the control group will receive standard routine diabetes care from their usual provider. Routine diabetes clinics are attended regularly (every 3 months) to provide diabetes care by a multi-disciplinary team (paediatric endocrinologist/paediatrician, diabetes nurse specialist, dietitian). Between scheduled study visits, participants will have the usual ability to contact the clinical team as is routine for all patients.
Participants in the control group will continue self-monitoring blood glucose using conventional finger stick blood glucose testing 4 to 6 times per day with a glucometer. No additional intervention will be provided during the 12-week primary study period. To maximize study recruitment, all participants will be invited (and reconsented) to continue in an open and supported 12-week extension phase where they will receive a flash glucose monitoring system.
Control group
Active

Outcomes
Primary outcome [1] 322018 0
The primary outcome is the change in glycated haemoglobin (HbA1c) between groups. HbA1c will be measured from a small whole blood sample by a calibrated point-of-care device (DCA Vantage Analyzer, Siemens Healthcare Diagnostics, Ireland).
Timepoint [1] 322018 0
Baseline, 12 weeks post baseline (the primary end point), 24 weeks post baseline
Secondary outcome [1] 377021 0
The change in time in target (time spent in target range 3.9 – 10 mmol/L). Time in target will be recorded from a report of data downloaded from the flash glucose monitoring system.
Timepoint [1] 377021 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [2] 377023 0
The change in time in hypoglycaemia (glucose <3.9 mmol/L). Time in hypoglycaemia will be recorded from a report of data downloaded from the flash glucose monitoring system.
Timepoint [2] 377023 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [3] 377024 0
The change in time in hyperglycaemia (glucose >10 mmol/L). Time in hyperglycaemia will be recorded from a report of data downloaded from the flash glucose monitoring system.
Timepoint [3] 377024 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [4] 377025 0
Glucose monitoring frequency (i.e., glucose level checks) will be assessed in both groups by recording the average finger pricks per day from personal glucometers and average scans per day as recorded by the flash glucose monitoring system.
Timepoint [4] 377025 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [5] 377026 0
The change in quality of life as measured by the Diabetes Quality of Life for Youth Scale (DQOLY)
Timepoint [5] 377026 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [6] 377027 0
The change in fear of hypoglycaemia as measured by the Hypoglycaemia Fear Survey for Children (HFSC)
Timepoint [6] 377027 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [7] 377028 0
The change in self-efficacy as measured by the Self-Efficacy for Diabetes Self-Management (SEDM) questionnaire
Timepoint [7] 377028 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [8] 377029 0
The change in parental fear of hypoglycaemia as measured by the Hypoglycaemia Fear Survey for Parents
Timepoint [8] 377029 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [9] 377030 0
The change in executive functioning as measured by the Diabetes-Related Executive Functioning Scale (DREFS).
Timepoint [9] 377030 0
Baseline, 12 weeks post-baseline, 24 weeks post baseline
Secondary outcome [10] 377031 0
Adverse events, including severe hypoglycaemia (child is having altered mental status and unable to assist in their care, or is semiconscious or unconscious), diabetic ketoacidosis (DKA), sensor failure, and cutaneous adverse events (e.g., pain, itching, redness, subcutaneous haemorrhage, infection). Adverse events will be reported by participants or a parent/guardian at study visits. Research staff will also phone participants every 4 weeks to collect data on adverse events.
Timepoint [10] 377031 0
4-, 8-, 12-, 16-, 20- and 24-weeks post-baseline
Secondary outcome [11] 377032 0
Flash glucose monitoring (FGM) performance (i.e., sensor problems, reader problems), will be self-reported using a non-validated instrument adapted from previous similar research. On an ordinal scale from 0 (strongly disagree) to 5 (strongly agree), participants will rate their opinion in regards to the following areas: acceptability of sensor application, wear/use of the device and comparison to self-monitoring blood glucose.
Timepoint [11] 377032 0
12 weeks post-baseline, 24 weeks post baseline

Eligibility
Key inclusion criteria
1. Children aged 4 to less than or equal to 13 years;
2. A diagnosis of T1D for 6 months or longer duration;
3. Current HbA1c greater than or equal to 58 mmol/mol and less than or equal to 110 mmol/mol;
4. On an insulin dose per day > 0.05 units of insulin/kg/day;
5. No regular use of flash glucose monitoring (FGM) or continuous glucose monitoring (CGM) in the previous 3 months.
Minimum age
4 Years
Maximum age
13 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
There will be no restriction on insulin regimen.

1. Any severe chronic diabetes-related complications;
2. Severe medical or psychiatric co-morbidity/severe mental illness;
3. Participation in another study that could affect glucose measurements;
4. Plans to leave study site regions prior to study completion;
5. Regular continuous use of FGM or CGM;
6. HbA1c > 110mmol/mol.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will be done by a biostatistician blinded to allocation arm and will use non-informative group codes until all planned analyses are completed.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Patients who give consent for participation and fulfil the eligibility criteria will be enrolled in the study and randomly allocated in batches using a 1:1 ratio to either the control group or the intervention group. As gender and pre-study HbA1c may significantly affect the primary outcomes, minimisation will be used (based on gender [male, female; HbA1c [58 to 74 mmol/mol, 75 mmol/mol or greater; 7.5 to 8.9%, 9.0% or greater]) and with a small random component (20%) along with randomly ordering the participants in each batch used to preserve allocation concealment.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be calculated for all variables. The primary outcome is the between-group change in HbA1c at 12 weeks. The primary analysis will follow the intent-to-treat principle with all participants analyzed in the group to which they were randomized, regardless of actual sensor wear. Additional analyses include: HbA1c, glucose monitoring frequency and adherence, episodes of moderate and severe hypoglycaemia, episodes of DKA, and psychosocial variables using Poisson and linear mixed models as appropriate. Statistical analysis will be performed using Stata software with two-sided p < 0.05 considered significant.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
19/10/2020
Actual
22/10/2020
Date of last participant enrolment
Anticipated
Actual
5/04/2022
Date of last data collection
Anticipated
Actual
28/10/2022
Sample size
Target
100
Accrual to date
Final
107
Recruitment outside Australia
Country [1] 22127 0
New Zealand
State/province [1] 22127 0
Auckland
Country [2] 22128 0
New Zealand
State/province [2] 22128 0
Northland
Country [3] 22129 0
New Zealand
State/province [3] 22129 0
Dunedin
Country [4] 22130 0
New Zealand
State/province [4] 22130 0
Bay of Plenty

Funding & Sponsors
Funding source category [1] 304314 0
Charities/Societies/Foundations
Name [1] 304314 0
Starship Foundation
Country [1] 304314 0
New Zealand
Primary sponsor type
Hospital
Name
Starship Children’s Health
Address
Private Bag 92024, Auckland 1142, New Zealand
Country
New Zealand
Secondary sponsor category [1] 304561 0
University
Name [1] 304561 0
Liggins Institute
Address [1] 304561 0
The University of Auckland, 2-6 Park Avenue, Grafton, Auckland 1023
Country [1] 304561 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304768 0
Health and Disability Ethics Committee
Ethics committee address [1] 304768 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 304768 0
New Zealand
Date submitted for ethics approval [1] 304768 0
24/01/2020
Approval date [1] 304768 0
10/04/2020
Ethics approval number [1] 304768 0
20/NTA/12

Summary
Brief summary
Flash continuous glucose monitoring (FGM) technology, could increase glucose monitoring and in turn diabetes control among children with T1D. FGM users attach a small sensor to their arm to monitor interstitial glucose levels. The sensor is worn for up to 2 weeks. They scan the sensor with a reader, which immediately displays 1) their current interstitial glucose level, as well as 2) a graph of retrospective glucose data for the previous 8 hours and 3) a glucose trend prediction arrow. Both retrospective and predicted glucose trends are not available with SMBG technology. FGM, therefore, can provide accurate and up-to-date glucose information, as well as being user-friendly (simple to scan the sensor, no limit to scanning frequency), provide rapid results and be discrete (scanning through clothing etc.); all allowing for marked increase frequency of testing.
We will conduct a randomized controlled trial to determine whether FGM can improve diabetes control in children with T1D aged 4-13, inclusive, who are not currently achieving adequate diabetes control. It is hypothesized at 12 weeks there will be a 7 mmol/mol greater improvement (reduction) in glycaemic control (HbA1c) in the intervention group compared to the change in glycaemic control in the control group
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 98138 0
A/Prof Craig Jefferies
Address 98138 0
1. Paediatric Diabetes and Endocrinology, Starship Children’s Health, Grafton, Auckland 1050
2. Liggins Institute, The University of Auckland, 2-6 Park Avenue, Grafton, Auckland 1023
Country 98138 0
New Zealand
Phone 98138 0
+64 21 957 877
Fax 98138 0
Email 98138 0
[email protected]
Contact person for public queries
Name 98139 0
Craig Jefferies
Address 98139 0
1. Paediatric Diabetes and Endocrinology, Starship Children’s Health, Grafton, Auckland 1050
2. Liggins Institute, The University of Auckland, 2-6 Park Avenue, Grafton, Auckland 1023
Country 98139 0
New Zealand
Phone 98139 0
+64 21 957 877
Fax 98139 0
Email 98139 0
[email protected]
Contact person for scientific queries
Name 98140 0
Craig Jefferies
Address 98140 0
1. Paediatric Diabetes and Endocrinology, Starship Children’s Health, Grafton, Auckland 1050
2. Liggins Institute, The University of Auckland, 2-6 Park Avenue, Grafton, Auckland 1023
Country 98140 0
New Zealand
Phone 98140 0
+64 21 957 877
Fax 98140 0
Email 98140 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?
De-identified data related to the primary and secondary outcomes.
When will data be available (start and end dates)?
Data will be available prior to submitting the first manuscript for publication (approximately May 2021) through 10 years after the youngest participant has turned 16 (approximately January 2042).
Available to whom?
Those involved in the peer review process for publication in a scientific journal, upon request.
Available for what types of analyses?
Those analyses performed to report the study findings.
How or where can data be obtained?
By emailing the lead investigator, A/Prof Craig Jefferies, craigj (at) adhb (dot) govt (dot) nz


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5773Ethical approval    378770-(Uploaded-17-06-2020-07-17-20)-Study-related document.pdf
6387Study protocolStyles S, Wheeler B, Boucsein A, et al. A comparison of FreeStyle Libre 2 to self-monitoring of blood glucose in children with type 1 diabetes and sub-optimal glycaemic control: a 12-week randomised controlled trial protocol. J Diabetes Metab Disord. 2021;20(2):2093-2101. Published 2021 Oct 5. doi:10.1007/s40200-021-00907-y   378770-(Uploaded-27-04-2021-12-52-19)-Study-related document.pdf
6388Informed consent form    378770-(Uploaded-27-04-2021-12-37-28)-Study-related document.doc



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Jefferies CA, Boucsein A, Styles SE, et al. Effect... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseA comparison of FreeStyle Libre 2 to self-monitoring of blood glucose in children with type 1 diabetes and sub-optimal glycaemic control: a 12-week randomised controlled trial protocol.2021https://dx.doi.org/10.1007/s40200-021-00907-y
N.B. These documents automatically identified may not have been verified by the study sponsor.