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Trial registered on ANZCTR


Registration number
ACTRN12619001551189
Ethics application status
Approved
Date submitted
24/10/2019
Date registered
11/11/2019
Date last updated
11/11/2019
Date data sharing statement initially provided
11/11/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
MiaoMiao continuous glucose monitoring in children affected by type 1 diabetes – a randomised cross over trial.
Scientific title
The MiaoMiao study: Can new more affordable diabetes technologies improve fear of hypoglycaemia in children and their parents affected by diabetes?
Secondary ID [1] 299620 0
None
Universal Trial Number (UTN)
U1111-1236-9189
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 314924 0
Condition category
Condition code
Metabolic and Endocrine 313280 313280 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The 17-week trial duration includes a 1 week run-in phase to collect baseline data followed by a 6-week phase during which the intervention group will commence the intervention and the control group will continue their usual glucose monitoring approach. This phase will be followed by a wash out period of 4 weeks to eliminate any carry-over effect. During the last phase, the participants will crossover between groups for an additional 6 weeks.

The standard Flash Glucose Monitoring (FGM) (Abbott FreeStyle Libre) which will be in use by all participants at study commencement (inclusion criteria) consists of an easy to apply, wear and use interstitial glucose sensor and glucose reader. The sensor is worn in the upper arm for up to 14 days. In addition to this pre-existing FGM, the intervention group will receive the MiaoMiao device which is a small cap that attaches directly to the FGM sensor. The MiaoMiao transmits sensor data via BluetoothTM to an app on the child’s phone or smartwatch (xDrip+/Spike/GLIMP/Tomato - depending on compatibility with the mobile device’s operating system). This displays continuous glucose data on the child’s mobile device. The parents/caregivers will also have the option of “following” this data on their smart phones as well as provide safety alarms in response to low or high glucose levels, even when not in Bluetooth™ range. It is anticipated that this data will be used to help children and their families make usual insulin dosing and other management decisions (replacing their use of FGM). No additional intervention will be provided during the 6-week intervention period (other than appropriate MiaoMiao CGMS training/technical support). All participants after completion of RCT will have the chance to keep their MiaoMiao transmitter. Adherence to the 6-week intervention can be measured by review of the relevant app data, which will be downloaded for analysis at completion of the intervention.
Intervention code [1] 315876 0
Behaviour
Intervention code [2] 315970 0
Lifestyle
Intervention code [3] 315971 0
Treatment: Devices
Comparator / control treatment
The participants allocated to the control group will continue using their self-funding flash glucose monitoring system.
Control group
Active

Outcomes
Primary outcome [1] 321768 0
Parental fear of hypoglycaemia as measured by Fear of Hypoglycemia Survey (parent version)
Timepoint [1] 321768 0
Primary endpoint - 6 weeks and 16 weeks post-baseline.
Secondary outcome [1] 376146 0
Child fear of hypoglycaemia as measured by Fear of Hypoglycemia Survey (child version)
Timepoint [1] 376146 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [2] 376147 0
Time in target (Time spent in target range 3.9 – 10 mmol/L) as measured by retrospective glucose readings downloaded from the flash glucose monitoring reader or app
Timepoint [2] 376147 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [3] 376148 0
Time spent >10mmol/L as measured by retrospective glucose readings downloaded from the flash glucose monitoring reader or app
Timepoint [3] 376148 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [4] 376149 0
Time spent > 15 mmol/L as measured by retrospective glucose readings downloaded from the flash glucose monitoring reader or app
Timepoint [4] 376149 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [5] 376150 0
Time spent in hypoglycaemia (glucose < 3.9 mmol/L) as measured by retrospective glucose readings downloaded from the flash glucose monitoring reader or app
Timepoint [5] 376150 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [6] 376151 0
Time spent in hypoglycaemia (glucose < 3.2 mmol/L) as measured by retrospective glucose readings downloaded from the flash glucose monitoring reader or app
Timepoint [6] 376151 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [7] 376152 0
Health-related quality of life as measured by the PedsQL 4.0 generic core scales
Timepoint [7] 376152 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [8] 376153 0
Diabetes-specific quality of life as measured by the PedsQL 3.2 diabetes module
Timepoint [8] 376153 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [9] 376154 0
Diabetes treatment satisfaction as measured by the Diabetes Treatment Satisfaction Questionnaire
Timepoint [9] 376154 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [10] 376155 0
PedsQL Family Impact module
Timepoint [10] 376155 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [11] 376156 0
Sleep as measured by actigraphy
Timepoint [11] 376156 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [12] 376157 0
Sleep as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) sleep questionnaire
Timepoint [12] 376157 0
6 weeks, 16 weeks post-baseline.
Secondary outcome [13] 376158 0
The adverse events that may relate to using MiaoMiao might include, but are not limited to, severe hypoglycaemia, diabetic ketoacidosis, skin irritations and reactions, MiaoMiao CGMS failure, loss of connectivity to phone, and sensor failure rates from baseline to the end of the trial period for each study group from baseline. These will be assessed by participant self-report as events occur as well as at study visits, and data-linkage to medical records.
Timepoint [13] 376158 0
6 weeks, 16 weeks post-baseline.

Eligibility
Key inclusion criteria
1) Aged 13 years and under with a parent/caregiver involved in diabetes management;
2) Already using flash glucose monitoring (FGM) technology with no restrictions based on insulin regimen;
3) Diagnosed with type 1 diabetes for at least 6 months;
4) Equal to or greater than 0.5 units of insulin/kg/day;
5) Plans to continue with routine clinical care during the whole period of the study;
6) Intention for continuous use of FGM during the whole study period
7) Currently residing in and expecting to remain in regions served by the Canterbury, Capital and Coast, Mid-central, South Canterbury, Auckland, and Southern District Health Boards for the following year.
8) Ability to understand study procedures, including English language proficiency, and to comply with them for the entire length of the study.
Minimum age
2 Years
Maximum age
13 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Already using MiaoMiao continuous glucose monitoring system (CGMS) or another CGMS product (other than FGM)
2) Any severe diabetes-related complications (nephropathy on treatment, retinopathy with associated visual loss – milder degrees will not be excluded);
3) Other severe uncontrolled medical or psychiatric co-morbidity/severe mental illness;
4) participation in another device or drug study that could affect glucose measurements during the study period;
5) Inability of a legal guardian to give written informed consent and/or provide day to day diabetes management input.
6) Plan to leave study regions prior to study completion.

Study design
Purpose of the study
Educational / counselling / training
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation will involve contacting the holder of the allocation schedule who will be offsite
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will be conducted via a remote internet-based service (www.sealedenvelope.com)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The outcome measure for which the study is powered is reduction of fear in hypoglycaemia. One study found standard deviations (SDs) for parent-reported HFS of 17 and 18 for two groups and another study found child-reported SDs of 14.2-15.2 over three different times. The later study also found test-retest reliabilities of 0.44 (over 13 weeks including an intervention) and 0.62 (over 12 weeks post intervention). Given the lack of other data in the literature, based on these values, we have assumed an overall correlation of r=0.52 for the purposes of determining the standard deviation of the difference of differences (based on combining r=0.6 and r=0.4). Using this, and assuming no intraclass correlation within sites for the difference of differences, 50 participants will be required in order to have 80% power to detect a difference of 8 points in change during the two treatment assuming a standard deviation of 20 for fear of hypoglycaemia at each of the four measurement occasions using a two-sided test at the 0.05 level. We will increase the number of the participants to 55 to account for approximately 10% missing data (e.g., data lost to periods of the child not wearing a sensor).

Appropriate descriptive statistics will be presented for all variables (including means and standard deviations for continuous normally distributed variables and counts and percentages for categorical variables).

The primary outcome is parental fear of hypoglycaemia and the primary analysis will follow the intent-to-treat principle with all participants analysed in the group to which they were randomised, regardless of actual MiaoMiao/FGM wear (with departures from pure intent-to-treat due to missing data at particular assessment times). The results will be analysed using linear mixed models for continuous outcomes (including the primary outcome of hypoglycaemia fear survey [HFS] scores) with a random participant-phase effect to incorporate the multiple measurements taken for study participants within each 6-week phase (once at the start and once at the end of that phase) and a random participant effect for the multiple measurements from each participant both using the MiaoMiao CGMS and then without this device. The centres will be modelled using a random effect, although we do not anticipate this having any effect on results.
The statistical models will include period effects to accommodate systematic changes during the study. Tests for washout will be performed. Standard model diagnostics will be used and log-transformations considered if model residuals are skewed, and mixed quantile regression (modelling medians) if this does not resolve issues with residuals. The number of adverse events is likely to be low and will be compared between conditions using signed Wilcoxon tests, which will ignore any clustering effects within centers. Missing data is unlikely to be substantial given our previous research but we have allowed for just under 10% loss to attrition in designing the study.

Additional sleep statistical analyses will be performed using linear mixed models as above to model sleep parameters, and related outcomes. The potential mediating effects of change in QOL, and fear of hypoglycaemia on sleep outcomes will be investigated as well as the potential mediating effects of change in sleep, QOL, and fear of hypoglycaemia outcomes.

Should higher levels of missing data eventuate, pattern mixture models will be used to explore the robustness of study findings under plausible scenarios of informative missing data. Statistical analysis will be performed using R 3.6.0 with two-sided p < 0.05 considered significant.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 21954 0
New Zealand
State/province [1] 21954 0
Auckland
Country [2] 21955 0
New Zealand
State/province [2] 21955 0
Canterbury
Country [3] 21956 0
New Zealand
State/province [3] 21956 0
Otago
Country [4] 21957 0
New Zealand
State/province [4] 21957 0
Southern
Country [5] 21958 0
New Zealand
State/province [5] 21958 0
South Canterbury
Country [6] 21959 0
New Zealand
State/province [6] 21959 0
Wellington
Country [7] 21960 0
New Zealand
State/province [7] 21960 0
Manawatu-Wanganui

Funding & Sponsors
Funding source category [1] 304097 0
Charities/Societies/Foundations
Name [1] 304097 0
Lottery Health
Address [1] 304097 0
Department of Internal Affairs
46 Waring Taylor Street
Wellington 6011
New Zealand
Country [1] 304097 0
New Zealand
Funding source category [2] 304099 0
University
Name [2] 304099 0
Department of Women's and Children's Health, Dunedin School of Medicine, University of Otago
Address [2] 304099 0
PO Box 56
Dunedin 9054
Country [2] 304099 0
New Zealand
Primary sponsor type
University
Name
Department of Women's and Children's Health, University of Otago
Address
PO Box 56
Dunedin 9054
Country
New Zealand
Secondary sponsor category [1] 304307 0
Hospital
Name [1] 304307 0
Southern District Health Board
Address [1] 304307 0
Dunedin Hospital 201 Great King St, Dunedin, 9016
Country [1] 304307 0
New Zealand
Secondary sponsor category [2] 304309 0
Hospital
Name [2] 304309 0
Capital and Coast District Health Board
Address [2] 304309 0
Riddiford St, Newtown, Wellington 6021
Country [2] 304309 0
New Zealand
Secondary sponsor category [3] 304310 0
Hospital
Name [3] 304310 0
Canterbury District Health Board
Address [3] 304310 0
The Princess Margaret Hospital PO Box 800 Christchurch 8140
Country [3] 304310 0
New Zealand
Secondary sponsor category [4] 304311 0
Hospital
Name [4] 304311 0
South Canterbury District Health Board
Address [4] 304311 0
High St, Parkside, Timaru 7910
Country [4] 304311 0
New Zealand
Secondary sponsor category [5] 304312 0
Hospital
Name [5] 304312 0
Auckland District Health Board
Address [5] 304312 0
2 Park Road, Grafton
Auckland 1023
Country [5] 304312 0
New Zealand
Secondary sponsor category [6] 304313 0
Hospital
Name [6] 304313 0
MidCentral DHB
Address [6] 304313 0
50 Ruahine St, Roslyn, Palmerston North 4442
Country [6] 304313 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304586 0
Health and Disability Ethics Committee
Ethics committee address [1] 304586 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 304586 0
New Zealand
Date submitted for ethics approval [1] 304586 0
17/07/2019
Approval date [1] 304586 0
26/09/2019
Ethics approval number [1] 304586 0
19/NTB/118

Summary
Brief summary
The randomised crossover trial will investigate the effectiveness of a flash glucose monitoring (FGM) system converted to a continuous glucose monitoring system (MiaoMiao CGMS) vs standard FGM in a real-world setting among children with type 1 diabetes. In total, 55 participants will be enrolled and randomised to either the intervention (MiaoMiao CGMS) or control group (standard FGM). After the first 6 week trial phase, there will be a 4 week washout period, followed by a further 6 week trail phase in which all participants will crossover to the other study group. We hypothesise that MiaoMiao CGMS will reduce parental and child fear of hypoglycemia.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97486 0
A/Prof Benjamin Wheeler
Address 97486 0
Department of Women's and Children's Health
University of Otago
PO Box 56
Dunedin 9054
Country 97486 0
New Zealand
Phone 97486 0
+64 27 4701980
Fax 97486 0
Email 97486 0
ben.wheeler@otago.ac.nz
Contact person for public queries
Name 97487 0
A/Prof Benjamin Wheeler
Address 97487 0
Department of Women's and Children's Health
University of Otago
PO Box 56
Dunedin 9054
Country 97487 0
New Zealand
Phone 97487 0
+64 27 4701980
Fax 97487 0
Email 97487 0
ben.wheeler@otago.ac.nz
Contact person for scientific queries
Name 97488 0
A/Prof Benjamin Wheeler
Address 97488 0
Department of Women's and Children's Health
University of Otago
PO Box 56
Dunedin 9054
Country 97488 0
New Zealand
Phone 97488 0
+64 27 4701980
Fax 97488 0
Email 97488 0
ben.wheeler@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
As New Zealand is a small country, an individual in a de-identified dataset could possibly be identified.
What supporting documents are/will be available?
Informed consent form
Ethical approval
How or where can supporting documents be obtained?
Type [1] 5454 0
Ethical approval
Citation [1] 5454 0
Link [1] 5454 0
Email [1] 5454 0
Other [1] 5454 0
Type [2] 5455 0
Informed consent form
Citation [2] 5455 0
Link [2] 5455 0
Email [2] 5455 0
Other [2] 5455 0
Summary results
No Results