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Trial registered on ANZCTR


Registration number
ACTRN12619000469112
Ethics application status
Approved
Date submitted
15/03/2019
Date registered
21/03/2019
Date last updated
17/03/2020
Date data sharing statement initially provided
21/03/2019
Date results information initially provided
17/03/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
FiASP vs. aspart using an advanced closed-loop system
Scientific title
Systems performance and glucose control using an advanced hybrid closed-loop system in type 1 diabetes: Insulin aspart vs. faster acting insulin aspart (FiASP)
Secondary ID [1] 297727 0
Nil
Universal Trial Number (UTN)
U1111-1217-1398
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 312053 0
Condition category
Condition code
Metabolic and Endocrine 310617 310617 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This randomised crossover study compares glucose control using an advanced hybrid closed-loop (A-HCL) system delivering faster acting insulin aspart (FiASP) vs. insulin aspart in adults with type 1 diabetes.

FiASP has a more rapid onset and shorter duration of insulin action, therefore may improve the responsive of a HCL system. There is limited data available regarding the use of FiASP in HCL systems.

Participants will be assigned in random order either FiASP or insulin aspart delivery for a six week duration each via the A-HCL system (Stage 1 and Stage 2). Stage 1 and Stage 2 will be separated by two weeks, during which the insulin assigned for Stage 2 will be delivered in open-loop (OL). Two meal interventions (missed meal bolus and delayed meal bolus) will be conducted each during both Stage 1 and 2, incorporating a 40g carbohydrate-containing meal at home for dinner. For the final week of the study (Stage 3), participants will revert to the insulin that they were assigned to in Stage 1 without a wash-out period in OL.

This study will consist of ~5 visits over approximately a period of ~17 weeks. All participants will be provided with study devices and receive education regarding their use. The HCL system has advanced closed-loop (CL) capability. It comprises a continuous glucose monitoring (CGM) device ie. glucose sensor with a small electrode placed under the skin to continuously measure interstitial glucose levels, coupled with an insulin pump containing a computerised automated insulin delivery algorithm. Glucose sensor information is transmitted to the insulin pump, and the dose of insulin is calculated by the algorithm and automatically delivered every 5 minutes to account for basal insulin requirements. Patient-initiated bolus insulin doses are still required for meals.

Twenty-four participants are planned to undertake the study at one clinical site. All procedures involving study participants will be undertaken by study doctors and research nurses. Participants will receive regular text message and phone call reminders during each stage of the study to ensure adherence.
Intervention code [1] 313968 0
Treatment: Drugs
Comparator / control treatment
Comparator treatment involves using insulin aspart in an A-HCL system.
Control group
Active

Outcomes
Primary outcome [1] 319468 0
Time spent with sensor glucose 3.9–10.0 mmol/L using uploaded CGM data
Timepoint [1] 319468 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [1] 368283 0
Time spent with sensor glucose <3.0mmol/L using uploaded CGM data
Timepoint [1] 368283 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [2] 368284 0
Time spent with sensor glucose <3.9mmol/L using uploaded CGM data
Timepoint [2] 368284 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [3] 368285 0
Time spent with sensor glucose 3.9–7.8 mmol/L using uploaded CGM data
Timepoint [3] 368285 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [4] 368286 0
Time spent with sensor glucose >10.0mmol/L using uploaded CGM data
Timepoint [4] 368286 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [5] 368287 0
Time spent with sensor glucose >13.9mmol/L using uploaded CGM data
Timepoint [5] 368287 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [6] 368288 0
Time spent with sensor glucose >16.7mmol/L using uploaded CGM data
Timepoint [6] 368288 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [7] 368289 0
Sensor glucose variability (standard deviation, coefficient of variation, mean amplitude of glucose excursions (MAGE)) using uploaded CGM data
Timepoint [7] 368289 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [8] 368290 0
Sensor glucose area under curve (AUC) > 10mmol/L using uploaded CGM data
Timepoint [8] 368290 0
1) Final 6 weeks of Stage 1 and Stage 2
2) During and 4 hours post-meal interventions eg. late meal-bolus; missed meal-bolus (specific to a particular intervention and aggregated)
Secondary outcome [9] 368291 0
Change in fructosamine levels from baseline, measured on serum assay.
Timepoint [9] 368291 0
End Stage 1 and Stage 2
Secondary outcome [10] 368292 0
Major hypoglycaemic episodes (n) defined as requiring third party assistance (self-reported)
Timepoint [10] 368292 0
Cumulative total of this outcome (n) will be analysed throughout each study period.
Secondary outcome [11] 368293 0
Episodes of ketosis (n) defined as a blood ketone level > 0.6mmol/L on finger-prick ketone testing
Timepoint [11] 368293 0
Cumulative total of this outcome (n) will be analysed throughout each study period.
Secondary outcome [12] 368294 0
Episodes of ketoacidosis (n) measured using finger-prick ketone testing and blood gas analysis in hospital
Timepoint [12] 368294 0
This will only occur if the participant becomes unwell, is ketotic on finger-prick ketone testing and admission to hospital is clinically indicated.

Cumulative total of this outcome (n) will be analysed throughout each study period.
Secondary outcome [13] 368295 0
Unscheduled exits from closed-loop (CL) (n) using uploaded CGM data
Timepoint [13] 368295 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3
Secondary outcome [14] 368296 0
Time (%) in CL using uploaded CGM data
Timepoint [14] 368296 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3
Secondary outcome [15] 368297 0
Total insulin delivery (units) using uploaded CGM data
Timepoint [15] 368297 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3
Secondary outcome [16] 368298 0
Sensor mean absolute relative difference (MARD) with glucose meter as a reference, using uploaded CGM and glucose meter data
Timepoint [16] 368298 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3
Secondary outcome [17] 368299 0
Insulin delivery line-set changes (n) using uploaded CGM data
Timepoint [17] 368299 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3
Secondary outcome [18] 368300 0
Line occlusion alarms (n) using uploaded CGM data
Timepoint [18] 368300 0
1) Final 6 weeks of Stage 1 and Stage 2
2) 1 week of Stage 3

Eligibility
Key inclusion criteria
Type 1 diabetes of >1 year duration
Stable on insulin pump therapy for >3 months
Proficient in carbohydrate counting
Continuous glucose monitoring (CGM) sensor experience
HbA1c <10.0%
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Pregnancy
eGFR <40ml/min/1.73m2
History of diabetic ketoacidosis or severe hypoglycaemia in the last 3 months
Diabetic gastroparesis

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 concealed from participants and site investigators during enrolment and study run-in, until the time of randomisation. Randomisation will occur using sealed opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using sealed opaque envelopes
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
This represents an exploratory trial to provide preliminary data on the A-HCL performance with FiAsp compared with insulin aspart. The participant numbers were determined for the initial feasibility study and therefore (n) for this opportunistic extension study has been predetermined.

Comparisons will be made using CGM data collected over each of the six weeks in A-HCL comprising Stage 1 and Stage 2 of the study. Analyses will be by paired t-test. CGM and safety parameters in Stage 3 will be compared with the last week of Stage 1 and Stage 2 to determine whether changing directly from FiAsp to insulin aspart or from insulin aspart to FiAsp without a period of OL run-in impacts A-HCL performance.

Recruitment
Recruitment status
Active, not 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 in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 13423 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 26025 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 302255 0
Hospital
Name [1] 302255 0
St Vincent's Hospital Melbourne
Address [1] 302255 0
41 Victoria Pde
Fitzroy VIC 3065
Country [1] 302255 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Medtronic Diabetes
Address
18000 Devonshire Street
Northridge CA 91325
Country
United States of America
Secondary sponsor category [1] 302116 0
Commercial sector/Industry
Name [1] 302116 0
Novo Nordisk Pharmaceuticals Pty Ltd
Address [1] 302116 0
Level 3, 21 Solent Circuit
Baulkham Hills
NSW 2153
Country [1] 302116 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302931 0
St Vincents Hospital Melbourne HREC
Ethics committee address [1] 302931 0
41 Victoria Pde
Fitzroy
VIC 3065
Ethics committee country [1] 302931 0
Australia
Date submitted for ethics approval [1] 302931 0
20/02/2019
Approval date [1] 302931 0
15/03/2019
Ethics approval number [1] 302931 0
HREC 005/19

Summary
Brief summary
An advanced hybrid closed-loop (A-HCL) insulin delivery system has shown safety and high time-in-range in a previous study. The use of a faster acting insulin aspart (FiASP) with a more rapid onset and shorter duration of insulin action compared to standard insulin aspart could improve the responsiveness of a HCL system. Limited data is available regarding the use of FiASP in HCL systems.

The aim is to compare glucose control using A-HCL delivering FiASP vs. insulin aspart. All participants will undertake the study over a 17 week period, completing 2 study stages in random order, each of 6 week duration 1) A-HCL with FiASP, 2) A-HCL with insulin aspart. Stage 3 will be a 1 week period, reverting back to the insulin formulation used in Stage 1 without a washout period.

Outcome measures include CGM time-in-range and time in hyperglycaemic and hypoglycaemic ranges; safety and system performance outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91886 0
Prof David O'Neal
Address 91886 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 91886 0
Australia
Phone 91886 0
+61 3 9231 2211
Fax 91886 0
Email 91886 0
dno@unimelb.edu.au
Contact person for public queries
Name 91887 0
Dr Melissa Lee
Address 91887 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 91887 0
Australia
Phone 91887 0
+61 3 9231 2211
Fax 91887 0
Email 91887 0
melissa.lee@svha.org.au
Contact person for scientific queries
Name 91888 0
Dr Melissa Lee
Address 91888 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 91888 0
Australia
Phone 91888 0
+61 3 9231 2211
Fax 91888 0
Email 91888 0
melissa.lee@svha.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary