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

Abstract

Purpose
Frequent glucose monitoring is necessary for optimal glycaemic control. Second-generation intermittently scanned glucose monitoring (isCGM) systems inform users of out-of-target glucose levels and may reduce monitoring burden. We aim to compare FreeStyle Libre 2 (Abbott Diabetes Care, Witney, U.K.) to self-monitoring of blood glucose in children with type 1 diabetes and sub-optimal glycaemic control.

Methods
This open-label randomised controlled trial will enrol 100 children (4–13 years inclusive, diagnosis of type 1 diabetes ≥ 6 months, HbA1c 58–110 mmol/mol [7.5–12.2%]), from 5 New Zealand diabetes centres. Following 2 weeks of blinded sensor wear, children will be randomised 1:1 to control or intervention arms. The intervention (duration 12 weeks) includes second-generation isCGM (FreeStyle Libre 2) and education on using interstitial glucose data to manage diabetes. The control group will continue self-monitoring blood glucose. The primary outcome is the difference in glycaemic control (measured as HbA1c) between groups at 12 weeks. Pre-specified secondary outcomes include change in glucose monitoring frequency, glycaemic control metrics and psychosocial outcomes at 12 weeks as well as isCGM acceptability.

Discussion
This research will investigate the effectiveness of the second-generation isCGM to promote recommended glycaemic control. The results of this trial may have important implications for including this new technology in the management of children with type 1 diabetes.

Trial registration
This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 19 February 2020 (ACTRN12620000190909p) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1237-0090).

Full text

Vol.:(0123456789)
1 3
Journal of Diabetes & Metabolic Disorders
https://doi.org/10.1007/s40200-021-00907-y
STUDY PROTOCOL
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
SaraStyles1 · BenWheeler2,3 · AlisaBoucsein2 · HamishCrocket4· MicheldeLange5· DanaSignal6,7 ·
EskoWiltshire8,9 · VickiCunningham10· AnitaLala11· WayneCuteld6,7 · MartindeBock12,13 ·
AnnaSerlachius14 · CraigJeeries6,7,15
Received: 1 April 2021 / Accepted: 23 September 2021
© The Author(s) 2021
Abstract
Purpose Frequent glucose monitoring is necessary for optimal glycaemic control. Second-generation intermittently scanned
glucose monitoring (isCGM) systems inform users of out-of-target glucose levels and may reduce monitoring burden. We
aim to compare FreeStyle Libre 2 (Abbott Diabetes Care, Witney, U.K.) to self-monitoring of blood glucose in children with
type 1 diabetes and sub-optimal glycaemic control.
Methods This open-label randomised controlled trial will enrol 100 children (4–13years inclusive, diagnosis of type 1
diabetes ≥ 6months, HbA1c 58–110mmol/mol [7.5–12.2%]), from 5 New Zealand diabetes centres. Following 2weeks of
blinded sensor wear, children will be randomised 1:1 to control or intervention arms. The intervention (duration 12weeks)
includes second-generation isCGM (FreeStyle Libre 2) and education on using interstitial glucose data to manage diabetes.
The control group will continue self-monitoring blood glucose. The primary outcome is the difference in glycaemic control
(measured as HbA1c) between groups at 12weeks. Pre-specified secondary outcomes include change in glucose monitoring
frequency, glycaemic control metrics and psychosocial outcomes at 12weeks as well as isCGM acceptability.
Discussion This research will investigate the effectiveness of the second-generation isCGM to promote recommended gly-
caemic control. The results of this trial may have important implications for including this new technology in the manage-
ment of children with type 1 diabetes.
Trial registration This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 19
February 2020 (ACTRN12620000190909p) and the World Health Organization International Clinical Trials Registry Plat-
form (Universal Trial Number U1111-1237-0090).
Keywords Children· Intermittently scanned continuous glucose monitoring· Glycaemic control· Type 1 diabetes·
FreeStyle Libre 2· Self-monitoring of blood glucose
Abbreviations
BG Blood glucose
BMI Body mass index
CGM Continuous glucose monitoring
DHB District health board
DKA Diabetic ketoacidosis
HbA1c Glycated haemoglobin
isCGM Intermittently scanned continuous glucose
monitoring
RCT Randomised controlled trial
SMBG Self-monitoring blood glucose
Background
In New Zealand, there are an estimated 2,500 youth aged
0–18years living with type 1 diabetes [1–3]. New Zealand
has one of the highest rates of paediatric diabetes in the
world, with the incidence growing annually [4]. Internation-
ally, only one in four children with diabetes achieve inter-
national standards of glycaemic control (HbA1c < 58mmol/
* Sara Styles
sara.styles@otago.ac.nz
* Craig Jefferies
craigj@adhb.govt.nz
Extended author information available on the last page of the article

Journal of Diabetes & Metabolic Disorders
1 3
mol [< 7.5%]) [5–7]. This increases their risk for short and
long-term diabetes complications as shown by the Diabetes
Care and Control Trial [8–10].
Frequent and timely self-monitoring of blood glucose
(SMBG) is essential for guiding diabetes management deci-
sions and keeping glucose levels in a safe range. Conven-
tional SMBG involves finger-stick blood tests six or more
times each day [11]. Children may infrequently perform
SMBG because of social pressure to not be seen as ‘differ-
ent’ [12], physical discomfort from pricking their fingers,
and the technology is not user friendly (requires multiple
steps to obtain a reading) [13].
Real-time continuous glucose monitoring (rtCGM) and
intermittently scanned CGM have significant advantages
over SMBG [14]. rtCGM systems use a subcutaneous glu-
cose sensor to transmit and display a continuous stream of
real-time interstitial glucose data to a pump/reader. Despite
rtCGM systems being an accurate and effective glucose
monitoring tool, like other diabetes technologies they are
costly which can limit, or lead to inequity in uptake, and
alarms can contribute to alarm fatigue and subsequent
discontinuation of rtCGM use [15–17]. An alternative to
rtCGM is intermittently scanned continuous glucose moni-
toring (isCGM) technology. isCGM involves applying a
small factory-calibrated sensor to the back of the upper arm
to detect interstitial glucose levels and then scanning the sen-
sor with a reader to immediately display the glucose level.
As with newer versions of rtCGM, isCGM technology pro-
vides accurate glucose information for up to 2weeks [18].
Randomised controlled studies and real-world data based on
first-generation isCGM use have found evidence of better
glycaemic control with use over a sustained period of time
[19, 20].
First-generation isCGM is highly acceptable to children
and young people with diabetes and their caregivers [21, 22].
The second-generation isCGM system (FreeStyle Libre 2) is
more accurate than the previous generation and additionally
provides personalisable hypoglycaemia and hyperglycaemia
alarms [23]. First-generation isCGM has been associated
with improved quality of life and improved glycaemic con-
trol over 3months in children ages 5–18years [24]. The
optional alarm feature in the second-generation system may
particularly benefit families of children with above recom-
mended HbA1c given the alarms prompt action to treat
above target glucose levels and provide peace of mind that
below target glucose levels will be detected. There is one
randomised controlled trial currently being conducted in
adult patients with type 1 diabetes in the UK [25]. However,
there are no randomised controlled trials of second-genera-
tion isCGM in paediatric patient populations. In adolescents
and young adults with type 1 diabetes, the first-generation
of isCGM was found to increase glucose monitoring com-
pared to SMBG, but this did not translate into significant
differences in glycaemic control (as measured by HbA1c)
between groups at 6months [26]. Given the ease of being
able to scan (even through clothing), the reduction in SMBG
testing and both hypoglycaemia and hyperglycaemia alarms,
second-generation isCGM may provide an important oppor-
tunity to help children and their families improve self-man-
agement behaviours [26].
The proposed trial aims to investigate the effectiveness
of the second-generation isCGM for reducing HbA1c in
children above the recommended glycaemic control target
compared to SMBG.
Methods
Study design
This research is comprised of a multisite 12-week ran-
domised, controlled, parallel-group trial. As shown in Fig.1,
100 children with type 1 diabetes will be randomised to
12weeks of standard care (control group) or standard care
plus isCGM (intervention group). The study was approved
by the Northern A Health and Disability Ethics Commit-
tee (ethics reference: 20/NTA/12) and Māori (indigenous
New Zealanders) Research Consultation Committees in each
region. Recruitment began in October 2020 and the study is
expected to be completed by December 2022.
Study procedures
Study population andrecruitment
The study will be conducted at 5 diabetes centres across
New Zealand. Participants will be paediatric patients
receiving standard diabetes care through district health
board (DHB) diabetes services (Auckland DHB, South-
ern DHB, Capital Coast DHB, Bay of Plenty DHB, and
Northland DHB). These diabetes services provide care
for approximately 500 + children in the study age range.
During routine clinical visits, eligible children will be
identified by their usual paediatric endocrinologist/diabe-
tologist/paediatrician and invited to participate. Inclusion
criteria are: diagnosis of type 1 diabetes ≥ 6months; age 4
to 13years inclusive; on > 0.5 units of insulin/kg/day; no
regular use of isCGM or CGM in the previous 3months;
and current HbA1c ≥ 58mmol/mol and ≤ 110mmol/mol,
on day of consent. Children will not be included if they are
diagnosed with any severe chronic diabetes related com-
plications or severe medical or psychiatric co-morbidity/
severe mental illness requiring ongoing treatment (e.g.,
diagnosed eating disorder); are participating in another
study that could affect glucose measurements; or have

Journal of Diabetes & Metabolic Disorders
1 3
plans to leave study site regions prior to study completion.
Written informed consent will be obtained from parents/
guardians, written informed assent will be obtained from
participants aged 7 to 13years, and verbal assent will be
obtained from participants aged 4 to 6years. Any par-
ticipant can withdraw (or be withdrawn by their parent or
guardian) from the study at any point.
Randomisation
Prior to study commencement, a randomisation table was
generated by a biostatistician using Stata 15.1 software and
pre-defined parameters (pre-study HbA1c [58 to 74mmol/
mol, or ≥ 75 mmol/mol; 7.5 to 8.9%, or ≥ 9.0%], study
site), and imported into the REDCap randomisation mod-
ule. REDCap is a secure, web-based application designed
to support data capture for research studies [27]. Partici-
pants will be randomised in a 1:1 ratio to either the control
(SMBG) group or the intervention (isCGM) group at Visit
2 by research staff using the randomisation module. Partici-
pants, investigators, and study staff will not be masked to
group allocation.
Control group
All participants will continue standard diabetes care from
their usual paediatric diabetes care provider. Routine diabe-
tes clinics are attended regularly (at least every 3months)
to provide diabetes care by a multi-disciplinary team (pae-
diatric endocrinologist/diabetologist/paediatrician, diabetes
nurse specialist, dietitian, psychologist). Between scheduled
study visits, participants will have the usual ability to con-
tact their clinical team as is routine for all patients. Control
group participants will continue SMBG using conventional
finger stick BG testing with a glucometer and be fitted with
a blinded isCGM, sensor, which they will wear for the first
and final 2weeks of the RCT.
Intervention group
The intervention consists of a FreeStyle Libre 2 isCGM
system (sensors, reader, USB cable, power adapter, user’s
manual, and quick start guide) and structured education from
trained research staff. Education will include sensor inser-
tion, interpreting the readings, and optimisation of insulin
dosages, if appropriate. The first sensor will be applied by
Fig. 1 Study design. CGM,
continuous glucose monitoring;
isCGM, intermittently scanned
continuous glucose monitoring;
SMBG, self-monitoring blood
glucose

Journal of Diabetes & Metabolic Disorders
1 3
research staff. Participants will insert the next sensor 14days
later under supervision (Visit 3) and for the remainder of
the study. Participants will be instructed to scan a minimum
of 6–10 times each day with no longer than 8h between
two scans. Research staff will set the initial recommended
reader settings to 3.9mmol/L (70mg/dL) and 15.0mmol/L
(270mg/dL). Research staff will access glucose data online
through LibreView, a secure, cloud-based system, to gen-
erate a report of participants’ average interstitial glucose
level, time above/in/below range, and scans per day at 2-,
4-, 8- and 12-weeks from isCGM commencement. If the
report shows time spent 'low' is > 4% or time spent 'very low'
is > 1% then the report will be forwarded to the participant's
clinical team for follow-up.
As a safety precaution, participants will be instructed to
perform SMBG to confirm their glucose level before thera-
peutic interventions or corrective action are taken if hypo- or
hyperglycaemic levels (≤ 4.0 or ≥ 14.0mmol/l) or symptoms
occur.
To prevent sensor loss prior to the end of the 14-day sen-
sor session, participants will be provided with either Rocka-
dex (pre-cut sports tape), Hypafix® (BSN medical GmbH,
Hamburg, Germany) or cohesive tape to be used to attach
the sensor securely in the event the adhesive becomes loose.
Procedures
At screening and enrolment (Visit 1, beginning of Week
1) a point of care HbA1c will be measured to confirm
eligibility. Date of diabetes diagnosis for subsequent cal-
culation of duration of diabetes (month and year will be
recorded when the exact date is unknown), current insulin
regimen, insulin dosing, HbA1c measurements in previous
6months, and co-morbidities will be recorded from elec-
tronic medical records. Diabetic ketoacidosis (DKA) [28]
and severe hypoglycaemia events (defined as a blood glucose
value ≤ 3.9mmol/L and resulting in loss of consciousness,
a call for an ambulance and/or admission to hospital, or use
of glucagon) in the past 6months will also be recorded from
electronic medical records to provide baseline estimates of
frequency for these events. All participants will start blinded
CGM (FreeStyle Libre Pro, Abbott) to continually measure
and store glucose level data for up to 14days [29]. This
glucose monitoring system uses similar sensor technology
to the FreeStyle Libre 2 system in the intervention; how-
ever, the Pro system masks all glucose data until it is down-
loaded at Visit 2. Participants with sensor data for at least
50% of the blinded wear period will be randomised at Visit
2. Questionnaires for the participant-reported outcomes will
be administered before randomisation and at the end of the
12-week RCT.
Outcome assessments
The primary outcome is the between group change in HbA1c
at 12-weeks (i.e., end of week 14 of study). The timing of
all assessments is presented in Table1. Trained research
staff will be responsible for completing assessments. Visit 2
measurements will be taken before randomisation.
* Pediatric Quality of Life Inventory (PedsQL) 3.2 Dia-
betes Module, Hypoglycaemia Fear Survey (HFS), Self-Effi-
cacy for Diabetes Self-Management (SEDM). ** Diabetic
ketoacidosis, moderate and severe hypoglycaemia, issues
related to glucose monitoring device use.
Demographics
A self-administered questionnaire will collect demographic
information including age, gender, ethnicity, address, and
education level. Participants may choose to select more than
one ethnicity; however, each person will be allocated to a
single ethnic group for the purposes of statistical analyses
that will be prioritised in the order of Māori, Pacific, Asian
and European/Other [30]. The address where the participant
lives more than 50% of the time will be used to assess their
New Zealand deprivation score, which is a validated index of
Table 1 Outcome assessments Assessment Prior to ran-
domisation
During RCT
(Weeks
5, 7 & 11)
End of RCT Ongoing
Demographics X
Anthropometry X
HbA1c X X
CGM metrics X X X
Glucose monitoring behaviour X X
isCGM acceptability X
Psychosocial assessments* X X
Acute type 1 diabetes complications** X

Journal of Diabetes & Metabolic Disorders
1 3
the relative socioeconomic deprivation of the area in which
an individual lives [31].
Anthropometry
Weight and height will be measured using standard proce-
dures and calibrated instruments. Weight will be measured
with a fixed scale (DigiTol, Toledo, Switzerland or simi-
lar) or portable scale (Tanita Corporation, Japan or simi-
lar) to the nearest 0.1kg, with shoes and heavy clothing
removed. Height will be measured to the nearest 0.1cm,
by wall-fixed stadiometer (Harpenden stadiometer, Holtain
Limited, Pembs, UK or similar) or a portable stadiometer
(Leicester Height Measure, Invicta Plastics Ltd., Oadby,
England). Height and weight will be used to calculate body
mass index (BMI)-z-scores using Centers for Disease Con-
trol and Prevention growth standards [32].
HbA1c
Glycated haemoglobin (HbA1c) will be measured by tra-
ditionally calibrated point-of-care instrument (DCA Van-
tage Analyzer, Siemens Healthcare Diagnostics, Ireland) at
all sites, which meets acceptance criteria of having a total
CV < 3% in the clinically relevant HbA1c range [33]. In the
event a value is > 130mmol/mol (> 14%, maximum reading
possible) the value will be recorded as 130.
isCGM glucose metrics
During all follow-up visits, all retrospective glucose read-
ings from the previous 2weeks will be downloaded from
the isCGM reader or LibreView. Hypoglycaemia (time
below target) will be recorded as percentage of time below
target (< 3.9mmol/L). Time in range will be recorded as
the percentage of time in the range (3.9–10.0mmol/L) [34,
35]. Hyperglycaemia (time above target) will be recorded
as percentage of time above target (> 10mmol/L). Glucose
levels < 3.9 mmol/L between 10pm and 7am (nocturnal
hypoglycaemia) will be reported to the appropriate diabetes
care provider for follow-up.
Glucose monitoring behaviour
Glucose monitoring behaviour will be defined as scanning
(intervention group) or SMBG (intervention and control
group), which will be determined by device downloads of
glucose monitoring device data.
isCGM acceptability
isCGM acceptability will be evaluated using a non-validated
instrument adapted from previous similar research [36]. On
an ordinal scale from 0 (strongly disagree) to 5 (strongly
agree), participants will rate their opinion regarding the fol-
lowing areas: acceptability of sensor application, wear/use
of the device and comparison to SMBG.
Psychosocial assessments
Psychosocial data and overall diabetes treatment acceptance
will be collected through validated self-report questionnaires
completed online using (REDCap Research Electronic Data
Capture) software and the order of administration will be
standardised to increase reliability. Together the question-
naires will take between 30 and 45min to complete at each
time point. All questionnaires will be administered in Eng-
lish. Clinical care teams will be notified if participants report
physical or mental health problems necessitating follow-up.
The 33-item Pediatric Quality of Life Inventory (Ped-
sQL) 3.2 Diabetes Module is a measure of diabetes-specific
health-related quality of life that assesses participant’s and
parent’s/guardian’s perceptions of the participant’s diabetes-
specific symptoms and management challenges during the
past month [37]. The PedsQL 3.2 Diabetes Module meas-
ures five domains: Diabetes Symptoms, Treatment Barri-
ers, Treatment Adherence, Worry and Communication. Par-
ticipant self-report forms are specific for ages 5–7, (young
child), 8–12 (child), and 13–14 (adolescent). The parent
proxy form is specific to ages 2–4 (toddler), 5–7 (young
child), 8–12 (child), 13–14 (adolescent). The PedsQL 3.2
Diabetes Module Diabetes Symptoms and Diabetes Manage-
ment Summary scores have demonstrated excellent measure-
ment properties and are recommended as useful standardised
patient-reported outcomes of diabetes symptoms and diabe-
tes management in clinical research in children with type 1
diabetes [37]. Items are rated from 0 (never a problem) to
4 (almost always a problem). Item ratings are then reverse
scored and linearly transformed to a 0–100 scale, with higher
scores reflecting a better quality of life.
The Hypoglycaemia Fear Survey for Children (HFSC) is
a 25-item instrument adapted from the adult HFS [38]. The
HFSC will be completed by children aged 6years and older.
Overall, higher scores reflect greater fear of hypoglycaemia,
a higher score on the Behaviour Subscale reflects a greater
tendency to avoid hypoglycaemia and/or its negative conse-
quences, and a higher score on the Worry Subscale indicates
more worry concerning episodes of hypoglycaemia and its
consequences. The CHFS has shown adequate internal con-
sistency (HFSC behaviour subscale alpha = 0.70; CHFS
worry subscale alpha = 0.89; and CHFS-Total alpha = 0.85)
[38]. HFSC worry subscale and total scores have been shown
to correlate significantly with other measures of anxiety
[38]. Total scores and subscale scores will be calculated as
z-scores standardised to the instrument-specific and baseline
means and standard deviations.

Journal of Diabetes & Metabolic Disorders
1 3
The Self-Efficacy for Diabetes Self-Management (SEDM)
is a 10-item self-report questionnaire for youth aged
10–16years that examines confidence to carry out self-care
behaviours and covers all the key areas of diabetes self-man-
agement [39]. The SEDM will be completed by participants
who are 10years and older. Participants are asked “How sure
are you that you can do each of the following, almost all the
time” and items are rated from 1 (not at all sure) to 10 (com-
pletely sure) and averaged. Higher scores indicate higher
self-efficacy. The SEDM has demonstrated good validity and
reliability (Cronbach’s alpha 0.9) [39].
At Visit 1, parents/guardians of enrolled participants who
provide written consent for their own participation in the
study will complete a short questionnaire collecting demo-
graphic characteristics (e.g., age, gender, education level,
and ethnicity). At the baseline and follow-up visits parents/
guardians will complete questionnaires to assess their per-
ceptions of their own fear of their child experiencing hypo-
glycaemia using the parent version of the scale [38].
Statistical analysis
A sample size of 88 (44 participants in each group) would
provide 80% power to detect a difference in changes in
HbA1c of 7mmol/mol (0.75%) between the intervention
and control group using standard deviation of 15mmol/mol
and correlation of 0.7 between repeated observations on
the same person and a two-sided test at the 0.05 level [26,
40]. This is a clinically important difference and similar to
other proven technologies such as insulin pumps or CGM.
To account for a small amount of missing data and loss to
follow-up, we will recruit a sample size of 100 (50 partici-
pants per group) at baseline.
The statistician will be blinded to allocation arm and will
use non-informative group codes until all planned analyses
are completed. Descriptive statistics will be calculated for
all variables. The primary analysis will follow the intention-
to-treat principle with all participants analysed in the group
to which they were randomised, regardless of actual sensor
wear. Additional analyses include: HbA1c, glucose moni-
toring frequency and adherence, episodes of moderate and
severe hypoglycaemia (as defined in Safety section below),
episodes of DKA, and psychosocial variables using Poisson
and linear mixed models as appropriate. Statistical analy-
sis will be performed using Stata software with two-sided
p < 0.05 considered significant.
Safety
For safety monitoring purposes, LibreView reports will
be produced at 2-, 4-, 8-, and 12-weeks from isCGM com-
mencement and checked for episodes of moderate (blood
glucose values ≤ 3.9mmol/L) and severe (child is having
altered mental status and unable to assist in their care or is
semiconscious or unconscious) hypoglycaemia. In the event
the proportion of ‘low’ values is > 4% or ‘very low’ values
is > 1% the report will be forwarded to the participant’s usual
diabetes care provider for follow-up. Sensor failure rates and
cutaneous adverse events (e.g., pain, itching, redness, sub-
cutaneous haemorrhage, infection) will be self-reported to
research staff at each visit or by phone call every four weeks
throughout the study. All adverse events will be recorded in
an Adverse Event form.
Participants will be asked to contact research staff imme-
diately (by sending a photo of their affected skin site, if
possible) if they notice a cutaneous issue associated with
wearing the sensor. Clinical research staff will then advise if
medical treatment is necessary. Participants will be referred
to their general practitioner or emergency department, as
appropriate, for management of medical events.
For more significant or persistent adverse events involv-
ing skin, a barrier product will be offered (e.g., Cavilon
spray, SkinTac™) or drug therapy (e.g., zinc ointment, Fen-
istil gel, or hydrocortisone cream) prescribed, and the partic-
ipant’s caregiver will be instructed to relocate the sensor to
another area of the skin such that the effects are maintained
at a tolerable level. Ultimately, the decision to continue or
discontinue the use of the FreeStyle Libre 2 when localised
skin symptoms occur will be made in consultation with the
participant.
An internal Safety Monitoring Committee will be notified
of severe adverse events (e.g., severe hypoglycaemia [BG
value ≤ 3.9mmol/L and resulting in loss of consciousness,
a call for an ambulance and/or admission to hospital, or use
of glucagon], DKA [being unwell due to hyperglycaemia
and high ketones, and requiring a visit to the doctor, emer-
gency room, or admission to hospital]) immediately after
being reported to research staff. The Committee will then
discuss any necessary action. Non-urgent events (moderate
events) will be reported to the lead investigator after being
reported to research staff. The internal Safety Monitoring
Committee will be comprised of clinical investigators (CJ,
BW, EW, AL, VC).
Data management
All study participants will be assigned a non-informative
study identification number. Only research staff and inves-
tigators will have access to the electronic study records for
the purposes of recording data and checking completeness of
data. Data will be recorded and stored electronically in RED-
Cap, which is securely hosted at the University of Otago.
Identifiable information (e.g., date of diagnosis, address,
date of birth) will not be stored in REDCap. Instead, age in
whole numbers and duration of diabetes in whole numbers
will be recorded in REDCap. Local sites will, however, hold

Journal of Diabetes & Metabolic Disorders
1 3
in locked Excel sheets their own participants with address
and contact details (phone number and emails), so that if
the local sites need to contact participants (for replacement
Libre 2 devices etc.) they can do so.
REDCap features (e.g., calendar and colour-coding forms
to indicate complete or missing data) will help ensure adher-
ence to timeframes, compliance to measurement procedures,
and completeness of data. Data will be routinely checked for
missing and/or erroneous values by the study coordinator.
At the end of the study, original data collection sheets and
written informed consent will be stored securely at the lead
site along with copies of all data collected electronically.
The lead investigator will retain an anonymised electronic
copy of the cleaned data set, with all identifying information
removed. The data set may be shared as part of the scientific
peer-review process or shared to conduct a meta-analysis
(e.g., impacts of flash glucose monitoring on glycaemic con-
trol). The electronic dataset will be destroyed 10years from
the end of the study.
Discussion
isCGM technology has the potential to significantly improve
diabetes control in children, and limited data is available
especially for the second-generation isCGM system. Increas-
ing time in range, reducing HbA1c, reducing burden, and
improving quality of life for children with this lifelong
chronic disease is important and improving glycaemic con-
trol reduces the risk of acute and chronic diabetes compli-
cations. If next generation isCGM is effective in an RCT, it
will then increase our ability to have this device available
and funded for children worldwide.
Author contributions CJ and BW were responsible for the study con-
cept, oversight during protocol development, and will be responsible
for the conduct of the study. VC, AL, MdB, MdL contributed to the
study design and provided expert opinion during protocol development
and funding application support. CJ, BW, EW, VC, and AL will facili-
tate recruitment of patients as lead regional investigators and will serve
as the internal Safety Advisory Committee. WC will assist in study
recruitment. CJ, SS, BW, HC, and DS were responsible for providing
expert opinion during protocol development and preparing the detailed
protocol with AB. MdL will be responsible for randomisation, statisti-
cal analyses, and the statistical interpretation of results. AS provided
expert opinion during protocol development and funding application
support, as well as to all aspects related to mental health. All authors
contributed to refinement of the study protocol and approved the final
manuscript.
Funding The study funder is The Starship Foundation (Auckland, New
Zealand). The funder and the isCGM manufacturer have no roles or
responsibilities in study design, conduct, data analysis and interpreta-
tion, or manuscript writing. Intervention supplies and blinded glucose
sensors were purchased commercially from the isCGM manufacturer.
Availability of data and material De-identified data related to the pri-
mary and secondary outcomes will be available to those involved in the
peer review process for publication in a scientific journal, upon request.
Code availability Not applicable.
Declarations
Conflict of interest The authors have no conflicts of interest to declare
that are relevant to the content of this article.
Ethics approval The protocol underwent Māori (indigenous New Zea-
landers) consultation, which fostered input into this study. The study
protocol was approved by the Northern A Health and Disability Ethics
Committee (ethics reference: 20/NTA/12). All district health boards
approved recruitment and conduct of the study at their site.
Consent to participate Written informed consent will be obtained from
parents/guardians, written informed assent will be obtained from par-
ticipants aged 7 to 13years, and verbal assent will be obtained from
participants aged 4 to 6years.
Consent for publication Not applicable.
Open Access This article is licensed under a Creative Commons Attri-
bution 4.0 International License, which permits use, sharing, adapta-
tion, distribution and reproduction in any medium or format, as long
as you give appropriate credit to the original author(s) and the source,
provide a link to the Creative Commons licence, and indicate if changes
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permitted by statutory regulation or exceeds the permitted use, you will
need to obtain permission directly from the copyright holder. To view a
copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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Authors and Aliations
SaraStyles1 · BenWheeler2,3 · AlisaBoucsein2 · HamishCrocket4· MicheldeLange5· DanaSignal6,7 ·
EskoWiltshire8,9 · VickiCunningham10· AnitaLala11· WayneCuteld6,7 · MartindeBock12,13 ·
AnnaSerlachius14 · CraigJeeries6,7,15
Ben Wheeler
ben.wheeler@otago.ac.nz
Alisa Boucsein
a.boucsein@otago.ac.nz
Hamish Crocket
hamish.crocket@waikato.ac.nz
Michel de Lange
michel.delange@otago.ac.nz
Dana Signal
danez_01@hotmail.com
Esko Wiltshire
esko.wiltshire@otago.ac.nz
Vicki Cunningham
vicki.Cunningham@northlanddhb.org.nz
Anita Lala
anita.lala@bopdhb.govt.nz
Wayne Cutfield
w.cutfield@auckland.ac.nz
Martin de Bock
martin.debock@otago.ac.nz
Anna Serlachius
a.serlachius@auckland.ac.nz
1 Department ofHuman Nutrition, University ofOtago,
Dunedin, NewZealand
2 Department ofWomen’s andChildren’s Health, University
ofOtago, Dunedin, NewZealand
3 Paediatrics, Southern District Health Board, Dunedin,
NewZealand
4 Health, Sport andHuman Performance, School ofHealth,
University ofWaikato, Hamilton, NewZealand
5 Centre forBiostatistics, Te Pokapū Tatauranga Koiora,
Division ofHealth Sciences, Dunedin, NewZealand
6 Paediatric Diabetes andEndocrinology, Starship Children’s
Health, Auckland, NewZealand
7 Liggins Institute, The University ofAuckland, Auckland,
NewZealand
8 Department ofPaediatrics andChild Health, University
ofOtago, Wellington,Wellington, NewZealand
9 Capital & Coast District Health Board, Wellington,
NewZealand
10 Northland District Health Board, Whangarei, NewZealand
11 Paediatrics, Bay ofPlenty District Health Board, Tauranga,
NewZealand
12 Department ofPaediatrics, University ofOtago,
Christchurch, NewZealand
13 Canterbury District Health Board, Christchurch,
NewZealand
14 Psychological Medicine, The University ofAuckland,
Auckland, NewZealand
15 Department ofPaediatrics andChild Health, University
ofOtago, Wellington, NewZealand
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