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Trial registered on ANZCTR


Registration number
ACTRN12619001340123
Ethics application status
Approved
Date submitted
12/09/2019
Date registered
30/09/2019
Date last updated
30/09/2019
Date data sharing statement initially provided
30/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Faster insulin aspart (FiASP) vs. apart using an advanced closed-loop system: Extension study evaluating meal-time glucose control
Scientific title
Systems performance and glucose control with the Medtronic advanced hybrid closed loop system (A-HCL) using insulin aspart vs faster acting insulin aspart (FiASP): Extension study evaluating meal-time glucose control
Secondary ID [1] 299263 0
Nil
Universal Trial Number (UTN)
Trial acronym
Linked study record
This is an extension study to ACTRN12619000469112.

Health condition
Health condition(s) or problem(s) studied:
type 1 diabetes 314399 0
Condition category
Condition code
Metabolic and Endocrine 312734 312734 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
An extension to the study ACTRN12619000469112.

This is a crossover study comparing 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 when challenged with different meal interventions.

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 particularly with varying meal sizes, composition and time of day.

The study will have 2 stages. During Stage 1 of this study, all participants will be infusing insulin aspart via the A-HCL system for a 11 week period. Meal challenges will be administered in a free living environment twice a week with compositions varying in terms of carbohydrate content (30 or 60g) and high or low glycaemic index and protein content. Participants will be asked to bolus insulin immediately prior to meals. Insulin boluses will vary between correct dose boluses and modified to under-dose.

Upon completion of Stage 1, there will be washout period of 1 week. All participants will then enter Stage 2 whereby FiASP will be infused via A-HCL for a 11 week period during which study activities, including meal tests and meal bolus administration will mirror those in Stage 1.

This study will consist of ~3 visits over a period of ~20 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.

It is anticipated that all twelve participants recruited into the main study ACTRN12619000469112 will be recruited into this extension study which will be conducted 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] 315550 0
Treatment: Drugs
Comparator / control treatment

Comparator treatment involves using insulin aspart in an A-HCL system.
Control group
Active

Outcomes
Primary outcome [1] 321372 0
Time spent with sensor glucose 3.9–10.0 mmol/L using uploaded CGM data
Timepoint [1] 321372 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [1] 374786 0
Time spent with sensor glucose 3.9-7.8 mmol/L using uploaded CGM data
Timepoint [1] 374786 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [2] 374787 0
Time spent with sensor glucose >10mmol/L using uploaded CGM data
Timepoint [2] 374787 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [3] 374788 0
Time spent with sensor glucose >13.9mmol/L using uploaded CGM data
Timepoint [3] 374788 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [4] 374789 0
Time spent with sensor glucose >16.7mmol/L using uploaded CGM data
Timepoint [4] 374789 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [5] 374790 0
Time spent with sensor glucose <3.9mmol/L using uploaded CGM data
Timepoint [5] 374790 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [6] 374791 0
Sensor glucose area under curve (AUC) > 10mmol/L using uploaded CGM data
Timepoint [6] 374791 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [7] 374792 0
Time spent with sensor glucose <3.0mmol/L using uploaded CGM data
Timepoint [7] 374792 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [8] 374793 0
mean sensor glucose using uploaded CGM data
Timepoint [8] 374793 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [9] 374794 0
Unscheduled exits from closed-loop (CL) (n) using uploaded CGM data
Timepoint [9] 374794 0
Total duration of study
Secondary outcome [10] 374795 0
Time (%) in CL using uploaded CGM data
Timepoint [10] 374795 0
Total duration of study
Secondary outcome [11] 374796 0
Total insulin delivery (units) using uploaded CGM data
Timepoint [11] 374796 0
Total duration of study
Secondary outcome [12] 374797 0
Insulin delivery administered for meal bolus/ autobasal/ autobolus (Units)
Timepoint [12] 374797 0
Total duration of study
Secondary outcome [13] 374798 0
Insulin delivery line-set changes (n) using uploaded CGM data
Timepoint [13] 374798 0
Total duration of study
Secondary outcome [14] 374799 0
Line occlusion alarms (n) using uploaded CGM data
Timepoint [14] 374799 0
Total duration of study
Secondary outcome [15] 374800 0
Sensor mean absolute relative difference (MARD) with glucose meter as a reference, using uploaded CGM and glucose meter data
Timepoint [15] 374800 0
Total duration of study
Secondary outcome [16] 375062 0
Glucose standard deviation using uploaded CGM data
Timepoint [16] 375062 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study
Secondary outcome [17] 375063 0
Glucose coefficient of variation using uploaded CGM data
Timepoint [17] 375063 0
1) 3-hour period post-high GI meals; 4 hour period post-mixed meals and 5 hour period for high fat and high protein meals
2)Total duration of study

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
Sex
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
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)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
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 ten weeks in A-HCL comprising Stage 1 and Stage 2 of the study. Analyses will be by paired t-test.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/12/2019
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14771 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 28003 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 303797 0
Hospital
Name [1] 303797 0
St Vincent's Hospital Melbourne
Country [1] 303797 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] 303919 0
Commercial sector/Industry
Name [1] 303919 0
Novo Nordisk Pharmaceuticals Pty Ltd
Address [1] 303919 0
Level 3, 21 Solent Circuit
Baulkham Hills
NSW 2153
Country [1] 303919 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304316 0
St Vincents Hospital Melbourne HREC
Ethics committee address [1] 304316 0
41 Victoria Pde
Fitzroy
VIC 3065
Ethics committee country [1] 304316 0
Australia
Date submitted for ethics approval [1] 304316 0
12/08/2019
Approval date [1] 304316 0
14/08/2019
Ethics approval number [1] 304316 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 meal-time glucose control using A-HCL delivering FiASP vs. insulin aspart. All participants will undertake the study over a 22 week period, completing 2 study stages, each of 11 week duration 1) A-HCL with insulin aspart, 2) A-HCL with FiASP. Each stage will be identical with respect to meal challenges (2 per week of differing meal compositions).

Outcome measures include CGM time-in-range and time in hyperglycaemic and hypoglycaemic ranges and system performance outcomes.

Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 96510 0
Prof David O'Neal
Address 96510 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 96510 0
Australia
Phone 96510 0
+61 3 9231 2211
Fax 96510 0
Email 96510 0
[email protected]
Contact person for public queries
Name 96511 0
Dr Melissa Lee
Address 96511 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 96511 0
Australia
Phone 96511 0
+61 3 9231 2211
Fax 96511 0
Email 96511 0
[email protected]
Contact person for scientific queries
Name 96512 0
Dr Melissa Lee
Address 96512 0
St Vincent's Hospital Melbourne
41 Victoria Parade
Fitzroy VIC 3065
Country 96512 0
Australia
Phone 96512 0
+61 3 9231 2211
Fax 96512 0
Email 96512 0
[email protected]

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 Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.