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Trial registered on ANZCTR


Registration number
ACTRN12621000556842
Ethics application status
Approved
Date submitted
9/04/2021
Date registered
12/05/2021
Date last updated
24/03/2024
Date data sharing statement initially provided
12/05/2021
Date results information initially provided
17/02/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Advanced hybrid closed loop/artificial pancreas for youth with type 1 diabetes using conventional injection therapy and high-risk glycaemic control
Scientific title
Effect of advanced hybrid closed loop/artificial pancreas on glycaemic control in youth with type 1 diabetes using conventional injection therapy and high-risk glycaemic control
Secondary ID [1] 303918 0
PROTOCOL NUMBER: 0003-AHCL
Universal Trial Number (UTN)
U1111-1263-6560
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 321503 0
Condition category
Condition code
Metabolic and Endocrine 319252 319252 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a single arm longitudinal study investigating advanced hybrid closed loop (AHCL) in youth with high-risk glycaemic control that have previously been using injectable insulin therapy. Following baseline assessments of blinded continuous glucose monitoring (CGM) for 14 days and a run-in period of 72 hours running as sensor augmented pump (SAP) with predictive low glucose monitoring (PLGM) to allow subjects to familiarize with the system and for control to be optimised, all subjects will then enter into a 12-month study period of using the insulin pump in its trial settings in Auto mode.
The initial 12-month study period is followed by a 12-month study extension where participants will switch from the study insulin pump to a Government-funded insulin pump (MiniMedTM AHCL insulin pump). The CGM devices (Guardian 4 sensor/transmitter system), which is currently not funded in Aotearoa New Zealand, will be provided to participants during the study extension. The treatment period for this single arm study is 24 months in total. Expected duration of subject participation is 25 months (14 days baseline assessments + 3 days run-in + 12 months treatment period + 12 months extension).
The single arm study intervention is the Medtronic MiniMed™ 780G AHCL insulin pump running in AHCL mode. In use with the continuous glucose monitoring (CGM) components (Medtronic’s newest generation Guardian 4 Sensor and Guardian 4 transmitter), the MiniMed™ 780G AHCL pump is capable of continuous insulin delivery at set and variable rates, and the monitoring of glucose levels via a sensor that is inserted in the interstitial fluid under the skin, including the detection of possible low or high blood glucose episodes. The pump also displays glucose values, storing this data so that it can be retrospectively analysed. The MiniMed™ AHCL insulin pump also includes the closed loop algorithm as part of the SmartGuard™ collection of features. SmartGuard™ is comprised of Manual Mode Low Management, which includes the Suspend On Low feature (suspends insulin delivery when a pre-set low sensor glucose [SG] threshold is reached), the Suspend Before Low feature (enables insulin to suspend 30 minutes before a pre-set low SG threshold is reached) and Auto Mode (hybrid closed loop) feature. The pump can also be used as a simple pump without CGM or as a SAP without use of the SmartGuard™ features. When Auto Mode is enabled, the sensor glucose values (SGVs) received by the pump from the CGM system will be used to automatically calculate the required insulin dose. It will then deliver insulin to the patient, at five-minute intervals, to achieve glycaemic control. With the AHCL system, subjects must still deliver bolus insulin for meals. In addition, the setting for active insulin must be programmed. Basal rates are set for periods of open loop therapy. When Auto Mode is not enabled, the user may use the Smart Guard™ Low Management features. Here, basal rate delivery will be suspended either when the SG has reached a programmed low threshold (Suspend on Low) or before the SGV has reached the programmed low threshold (Suspend before Low).
Participants will receive face-to-face education at the study site by trained study staff (research nurses with diabetes knowledge who are insulin pump education specialists) based on the manufacturer's user guides. The initial educational session will take approximately 5-6 hours, including the device set-up of the pump. Participants’ pump data will be automatically uploaded to CareLink through the MiniMed™ Clinical mobile phone app, which will be installed on participants’ phones and is connected with the pump via Bluetooth. The app uploads data every 24 hours into the cloud, where study staff can review the data and give feedback to refine pump settings if necessary. These refinements are personalised based on the participant’s uploaded data and will happen after each review of the uploaded pump data. Remote reviews will happen daily for 7 days after initiation of AHCL, then weekly for 6 weeks, then monthly until the end of the study. Personalised pump setting changes/refinements can be insulin basal rates and insulin-to-carbohydrate-ratios, if required, and will be verified by the investigative staff by way of electronic review of the pump upload with the new settings.
Intervention code [1] 320224 0
Treatment: Devices
Intervention code [2] 320225 0
Lifestyle
Comparator / control treatment
This is a single arm study.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 327133 0
Glycaemic control as measured by percentage of time in range (3.9 – 10mmol/L), by way of CGM data analysis.
Timepoint [1] 327133 0
Baseline, 16 weeks post baseline.
Secondary outcome [1] 393909 0
Glycaemic control as measured by glycated haemaglobin (HbA1C)
Timepoint [1] 393909 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [2] 393910 0
Glycaemic outcomes via CGM data for % CGM time <3.0mmol/L
Timepoint [2] 393910 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [3] 393911 0
Glycaemic outcomes via CGM data for % CGM time <3.9mmol/L
Timepoint [3] 393911 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [4] 393912 0
Glycaemic outcomes via CGM data for % CGM time >10.0mmol/L
Timepoint [4] 393912 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [5] 393913 0
Glycaemic outcomes via CGM data for % CGM time >13.9mmol/L
Timepoint [5] 393913 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [6] 393914 0
Glucose levels during the day (0600-2359 hours), determined from CGM data.
Timepoint [6] 393914 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [7] 393915 0
Qualitative interview-based assessment of participant experience using AHCL
Timepoint [7] 393915 0
After 13 weeks of pump use in Auto mode (week 16 of total study duration)
Secondary outcome [8] 393916 0
The change in quality of life as measured by the Pediatric Quality of Life Inventory (PedsQL) Generic Scale
Timepoint [8] 393916 0
Baseline, 55 weeks post baseline
Secondary outcome [9] 393917 0
The change in diabetes-specific quality of life as measured by the PedsQL Diabetes Module
Timepoint [9] 393917 0
Baseline, 55 weeks post baseline
Secondary outcome [10] 393918 0
The change in fear of hypoglycaemia as measured by the Hypoglycaemia Fear Survey (HFS)
Timepoint [10] 393918 0
Baseline, 55 weeks post baseline
Secondary outcome [11] 393919 0
The change in diabetes treatment satisfaction as measured by the Diabetes Treatment Satisfaction Questionnaire-status (DTSQs)
Timepoint [11] 393919 0
Baseline, 55 weeks post baseline
Secondary outcome [12] 393920 0
The change in sleep quality, as measured by the Pittsburgh Sleep Quality Index (PSQI)
Timepoint [12] 393920 0
Baseline, 55 weeks post baseline
Secondary outcome [13] 395158 0
Glucose levels during the night (0000-0559 hours), determined from CGM data.
Timepoint [13] 395158 0
Baseline, and at 3 weeks, 16 weeks, 29 weeks, 42 weeks, 55 weeks, 68 weeks, 81 weeks, 94 weeks, and 107 weeks post baseline.
Secondary outcome [14] 406034 0
The change in feelings towards automated insulin dosing systems as measured by the INSPIRE survey.
Timepoint [14] 406034 0
Baseline, 55 weeks post baseline

Eligibility
Key inclusion criteria
1. Male or female aged 13 – 25 years inclusive.
2. Type I diabetes as per the American Diabetes Association Classification, diagnosed at least 1 year prior to Study Day 1.
3. Current HbA1c level of greater than or equal to 8.5% (69mmol/mol).
4. Not on insulin pump therapy prior to trial.
5. Minimum daily insulin requirement of greater than or equal to 0.5 units of insulin/kg/day.
6. Willing and able to adhere to the study protocol.
7. Access to the internet and a computer system that meets requirements for uploading the study pump.
Minimum age
13 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Use of a medication indicative of diabetes complications (ACE inhibitors and statins are permitted).
2. Use of systemic glucocorticoids within 2 weeks prior to the Baseline visit.
3. Current use of SGLT-2 or GLP-1 medications.
4. Use of Hydroxyurea.
5. History or current evidence of significant seizure disorder, renal impairment or cardiovascular disease (including uncontrolled hypertension), in the opinion of the Investigator.
6. History of severe visual impairment, in the opinion of the Investigator.
7. If female, is pregnant or plans to become pregnant while participating in the study. A positive urine pregnancy test at Screening is exclusionary.
8. Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Allocation is not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
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
Efficacy
Statistical methods / analysis
This study has a primary endpoint comparing Time in Range (TIR) from 14 days blinded baseline CGM data to the final two weeks of the AHCL use intervention after 3 months. Data will be presented as mean changes and standard deviations.
Power: Data from a recent AHCL regulatory study conducted by our group in well controlled participants aged 14-21 years showed improvement in TIR of 15.6% +/- 9.0%. Therefore, to determine the mean change in TIR to a 95% precision interval of +/- 4%, a sample size of 20 is required. Descriptive statistics will be calculated for all variables. The primary outcome is mean change in TIR from baseline to end of the intervention. Additional outcomes include: standard glycaemic metrics, HbA1c 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
5/07/2021
Actual
6/10/2021
Date of last participant enrolment
Anticipated
Actual
1/02/2022
Date of last data collection
Anticipated
28/02/2024
Actual
31/12/2023
Sample size
Target
20
Accrual to date
Final
20
Recruitment outside Australia
Country [1] 23589 0
New Zealand
State/province [1] 23589 0
Otago, Canterbury

Funding & Sponsors
Funding source category [1] 308305 0
Charities/Societies/Foundations
Name [1] 308305 0
NZ Lottery Grants Board
Country [1] 308305 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
362 Leith Street
North Dunedin
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 309109 0
None
Name [1] 309109 0
Address [1] 309109 0
Country [1] 309109 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 308281 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 308281 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 308281 0
New Zealand
Date submitted for ethics approval [1] 308281 0
27/01/2021
Approval date [1] 308281 0
25/03/2021
Ethics approval number [1] 308281 0
21/STH/33

Summary
Brief summary
The primary objective of this single arm longitudinal study is to explore the effectiveness of an advanced hybrid closed loop (AHCL) system among youth (previously using conventional injectable insulin therapy) with type 1 diabetes and a history of high-risk glycaemic control over 12 months in a real world setting. Further outcomes will explore psychological assessments and sleep quality. 20 volunteers aged 13-25 years with type 1 diabetes using conventional injection therapy and with high-risk glycaemic control will take part in the study. After baseline assessments and a run-in period, the subjects will then undergo a 12-month period of using the insulin pump in its trial settings. The new insulin delivery method being tested in all patients in this study is the Medtronic MiniMed AHCL system running in Auto mode. This is followed by 1 12-month extension phase. Expected duration of subject participation is 25 months (12 months + 17 days baseline assessments and run-in + 12 months extension). The study will be conducted at study sites in Otago and Canterbury.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 110166 0
A/Prof Benjamin J Wheeler
Address 110166 0
Department of Women's and Children's Health
Otago Medical School - Dunedin Campus
PO Box 56
Dunedin 9054
New Zealand
Country 110166 0
New Zealand
Phone 110166 0
+64 3 474 0999
Fax 110166 0
Email 110166 0
[email protected]
Contact person for public queries
Name 110167 0
Benjamin J Wheeler
Address 110167 0
Department of Women's and Children's Health
Otago Medical School - Dunedin Campus
PO Box 56
Dunedin 9054
New Zealand
Country 110167 0
New Zealand
Phone 110167 0
+64 3 474 0999
Fax 110167 0
Email 110167 0
[email protected]
Contact person for scientific queries
Name 110168 0
Benjamin J Wheeler
Address 110168 0
Department of Women's and Children's Health
Otago Medical School - Dunedin Campus
PO Box 56
Dunedin 9054
New Zealand
Country 110168 0
New Zealand
Phone 110168 0
+64 3 474 0999
Fax 110168 0
Email 110168 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 December 2023) through 10 years after the youngest participant has turned 16 (approximately January 2035).
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 Ben Wheeler ([email protected])


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
11328Study protocol  [email protected]
11329Informed consent form  [email protected]
11330Ethical approval  [email protected]



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Boucsein, A et al. “Impact of Advanced Hybrid Clos... [More Details]
Study results articleYes Michaels VR, Boucsein A, Watson AS, Frewen CM, San... [More Details]

Documents added automatically
No additional documents have been identified.