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Trial registered on ANZCTR


Registration number
ACTRN12617001294347p
Ethics application status
Submitted, not yet approved
Date submitted
31/08/2017
Date registered
7/09/2017
Date last updated
7/09/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
The function and usability of two hybrid closed loop systems in patients aged 13 - 25 years with type 1 diabetes during a 7 day hotel study.
Scientific title
Function and usability of two hybrid closed loop systems in outpatients with type 1 diabetes
Secondary ID [1] 292786 0
None
Universal Trial Number (UTN)
U1111-1201-5702
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 304596 0
Condition category
Condition code
Metabolic and Endocrine 303922 303922 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Random allocation to either the Minimed Medtronic 670G Version 3.0, or Minimed Medtronic 670G Version 3.1.hybrid closed loop systems.

The study will compare the MiniMedTM 670G insulin pump version 3.0, coupled with a 4th generation glucose sensor and GST3C transmitter, to the MiniMedTM 670G insulin pump v 3.1+ UmaxCB version. The insulin pump and glucose sensor are both external devices, that have a subcutaneous infusion site (the pump), or a sampling foil that is subcutaneously embedded as part of the sensor. Insulin pumps are worn anywhere on the body, with the infusion site inserted into subcutaneous tissue, usually the abdomen or buttocks. Glucose sensors are worn anywhere there is enough subcutaneous tissue, usually the abdomen or buttocks.
The closed loop algorithm is contained in the MiniMedTM 670G series, using a modified proportional integrative derivative (PID) model, with insulin feedback and additional safety features. The algorithm receives (continuous glucose monitoring) CGM data every 5 minutes, and a “basal rate” insulin delivery is computed and adjusted every five minutes. Therefore, standard “basal” insulin that is pre-programmed in regular insulin pump therapy is replaced by the algorithm derived insulin delivery (given as a micro-bolus every 5 minutes). Meals will still be announced, and an insulin bolus delivered according to the individualised patient carbohydrate ratio and insulin sensitivity factor (should a correction bolus be required in addition to the insulin for carbohydrate).
The differences between V3.0 and version 3.1 are that the version 3.1 can calculate an insulin bolus for hyperglycaemia correction, and has more tolerable parameters for staying in automode,



All participants will have the intervention to manage their blood glucose levels for 7 days and nights, in a supervised outpatient environment (resort facility). Participants will not be restricted during the 7 days, and will just be observed.

Participants are required to perform capillary glucose testing 4 -6 times a day, and supervising staff will perform 2 tests overnight. All test values will be used to calibrate the sensors.
Participants will undergo two challenges to the hybrid system: unannounced lunch (i.e no insulin bolus given for the carb), and 60 minutes of moderate intensity exercise (jogging or cycling). The exercise challenge will occur after breakfast on day 6. The carbohydrate meal challenge will occur at lunch on day 6.

Adherence is defined as time spent in automode and is an important outcome measure. There will be no efforts to improve fidelity, as this is designed to be real world experience assessment of the technology function.
Intervention code [1] 299029 0
Treatment: Devices
Comparator / control treatment
All participants will receive an intervention, either the Minimed Medtronic 670G Version 3.0, or Minimed Medtronic 670G Version 3.1. Version 3.0 will be considered as the comparator/control, and version 3.1 as the intervention/experimental
Capillary glucose value on the recorded CONTOUR® NEXT LINK 2.4 glucometer, which is coupled to the 670G insulin pump. These values are used to calibrate the sensor, and are used as a reference standard for sensor accuracy.
Control group
Active

Outcomes
Primary outcome [1] 303261 0
Percent time the hybrid closed loop system is in automode while using the 670G3.0 verses 670G 3.1
Timepoint [1] 303261 0
Over the 7 days from the start of the intervention phase to the end of the study.
Primary outcome [2] 303290 0
Number of times the system reverts to regular insulin pump settings using the 670G 3.0 compared to 670G 3.1
Timepoint [2] 303290 0
A total count for the 7 days from the start of the intervention period to the end of the study. Expressed as a mean reverts per day per patient.
Primary outcome [3] 303291 0
Number of carbohydrate rescues for mild hypoglycaemia using the 670G 3.0 Vs 670G 3.1
Timepoint [3] 303291 0
A total count for 7 days from the beginning of the intervention to the end of the study. Expressed as a mean per day per patient.
Secondary outcome [1] 338462 0
Average sensor glucose value and standard deviation
Timepoint [1] 338462 0
For the 7 day study
Secondary outcome [2] 338463 0
Percent time spent in target sensor glucose range (3.9 - 10mmol/L.
Timepoint [2] 338463 0
Over the 7 days, divided in 24hour, Daytime (6am to midnight) and overnight (midnight to 6am)
Secondary outcome [3] 338464 0
Postprandial (3 hours after meal) area under the curve sensor glucose value
Timepoint [3] 338464 0
For every meal of the 7 day intervention period, and expressed as a mean postprandial meal excursion.
Secondary outcome [4] 338465 0
Area under the curve and glucose sensor reading above 10mmol/L,
Timepoint [4] 338465 0
Calculated over the 7 days from the beginning of the intervention period to the study end. Expressed as a mean per day.
Secondary outcome [5] 338466 0
Area under the curve of sensor glucose readings below 2.8mmol/L
Timepoint [5] 338466 0
Calculated over the 7 days from the beginning of the intervention period to the study end. Expressed as a mean per day.
Secondary outcome [6] 338532 0
This is another primary outcome:

Number of alarms that the system generates (670G 3.0 Vs 670G 3.1)
Timepoint [6] 338532 0
Recorded for 7 days from the beginning of the intervention until the study end, expressed as a mean per day per patient
Secondary outcome [7] 338533 0
This is another primary outcome:

Number and antecedent causes of hypoglycamia (for example algorithm determined, exercise, or inaccurate carbohydrate counting) while using the 670G 3.0 Vs 670G 3.1
Timepoint [7] 338533 0
Recorded over the 7 days from the beginning of the intervention until the end of the study. Expressed as number per day per patient.
Secondary outcome [8] 338534 0
This is another primary outcome:

Total daily insulin using the 670g 3.0 Vs 670G 3.1
Timepoint [8] 338534 0
Mean daily daily dose recorded for 7 days from the beginning of the intervention to the end of the study. Expressed as units/kg/day
Secondary outcome [9] 338535 0
This is another primary outcome


"Hybrid Closed Loop System Questionnaire", as developed specifically for hybrid closed loop studies, , using the 670g 3.0 Vs 670G version 3.1
Timepoint [9] 338535 0
Conducted at the conclusion of the 7 day trial
Secondary outcome [10] 338536 0
This is another primary outcome:

User diary (daily experience); a journal filled out by the participants using the 607g 3.0 and 670G 3.1. Participants will be asked to enter positive and negative experiences they encountered each day with respect to the system they are wearing
Timepoint [10] 338536 0
The diary will be completed daily. At the end of 7 days the journals will be collected and analysed, identifying key themes.
Secondary outcome [11] 338537 0
This is another primary outcome:


Semi structured interview during the study comparing overall experiences using the 670G 3.0 and 670G 3.1.
Timepoint [11] 338537 0
This will occur at the conclusion of the 7 day intervention study.
Secondary outcome [12] 338538 0
Area under the curve and glucose sensor reading above 13 mmol/L
Timepoint [12] 338538 0
Calculated over the 7 days from the beginning of the intervention period to the study end. Expressed as a mean per day.
Secondary outcome [13] 338539 0
Area under the curve and glucose sensor reading above 16mmol/L
Timepoint [13] 338539 0
Calculated over the 7 days from the beginning of the intervention period to the study end. Expressed as a mean per day.
Secondary outcome [14] 338540 0
Area under the curve of sensor glucose readings below 3.3mmol/L
Timepoint [14] 338540 0
Calculated over the 7 days from the beginning of the intervention period to the study end. Expressed as a mean per day.

Eligibility
Key inclusion criteria
1. Type 1 Diabetes duration > 1 year since diagnosis
2 Pump therapy for at least 6 months and Experience with sensor use
3. Age 13 - 25
4. 7.0% >A1C <10% at time of screening visit
5. willing to follow study instructions
6. Willing to perform at least 3 finger stick blood glucose measurements daily
7. willing to perform required sensor calibrations
8. Patient capable of reading and understand instructions in English
Minimum age
13 Years
Maximum age
25 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Subject is unable to tolerate tape adhesive in the area of sensor placement
2. Subject has any unresolved adverse skin condition in the area of sensor or device placement (e.g., psoriasis, rash, Staphylococcus infection)
3. Subject is actively participating in an investigational study (drug or device) wherein they have received treatment from an investigational study drug or device in the last 2 weeks
4. Subject has a positive pregnancy screening test
5. Subject is female, sexually active without the use of contraception, and plans/able to become pregnant during the course of the study and is not using an acceptable method of contraception
6. Subject has had a hypoglycemic seizure within the past 6 months prior to screening visit
7. Subject has had hypoglycemia resulting in loss of consciousness within the past 6 months prior to screening visit
8. Subject has had an episode of diabetic ketoacidosis (DKA) within the past 6 months prior to screening visit
9. Subject has a history of a seizure disorder
10. Subject has central nervous system or cardiac disorder resulting in syncope

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)
Sealed Opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer sequence generation
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Data will be analysed using using Stata/IC (version 13.0).

All glycaemic data will be presented as mean (SD) or count as applicaple. Functionality (for example number of automode kickouts, number of carbohydrate rescues ,number of alarms will be presented as count data.

Sensor performance will be assessed comparing the mean absolute relative difference of the sensor glucose compared to the capillary glucose value on the recorded CONTOUR® NEXT LINK 2.4 glucometer. For each study arm, sensor glucose values will be presented as mean and standard deviation – data that will be used to inform future studies

Qualitative data generated from the daily journal will be organised and coded by the research team; recurrent themes will be identified and presented.

The quantitative and qualitive data will be used to generate hypotheses and facilitate the ability to make power calculatations to test in larger studies planned in the future.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/09/2017
Actual
Date of last participant enrolment
Anticipated
23/09/2017
Actual
Date of last data collection
Anticipated
7/10/2017
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 8946 0
Princess Margaret Hospital - Subiaco
Recruitment postcode(s) [1] 17318 0
6008 - Subiaco

Funding & Sponsors
Funding source category [1] 297418 0
Government body
Name [1] 297418 0
NHMRC
Country [1] 297418 0
Australia
Funding source category [2] 297425 0
Charities/Societies/Foundations
Name [2] 297425 0
Juvenile Diabetes Research Foundation
Country [2] 297425 0
Australia
Primary sponsor type
Hospital
Name
princess Margaret Hospital
Address
1 Roberts Road, Subiaco, Perth, Western Australia, 6008
Country
Australia
Secondary sponsor category [1] 296419 0
None
Name [1] 296419 0
none
Address [1] 296419 0
none
Country [1] 296419 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 298524 0
Princess Margaret Hospital
Ethics committee address [1] 298524 0
Princess Margaret Hospital Health Research Ethics Committee
Princess Margaret Hospital
1 Roberts Road
Subiaco
Perth
Western Australia 6008
Ethics committee country [1] 298524 0
Australia
Date submitted for ethics approval [1] 298524 0
16/08/2017
Approval date [1] 298524 0
Ethics approval number [1] 298524 0

Summary
Brief summary
Hybrid closed loop (HCL) systems for the treatment of type 1 diabetes are rapidly advancing, particularly with respect to the algorithms that are used to calculate the automated insulin delivery. Hybrid closed loop systems consists of an insulin pump, a continuous glucose monitor, and an algorithm that determines the rate of insulin delivery between meals. Meals are still required to be announced by the user, and an insulin bolus proportional to the carbohydrate ingested is delivered according to an individualised carbohydrate ratio. The first commercially available HCL system has been FDA approved and is available in the United States. However, ongoing enhancements are required to improve glycaemic outcomes and patient user experience.
We will conduct a single-center pilot study, that is randomized, two arm parallel group in design in a hotel setting for 7 days, in subjects with type 1 diabetes on insulin pump therapy. Patients aged 13-25 years will be randomized in 2 groups to either use the 670G 3.0 system or the 670G 3.1+UmaxCB system. The objective is to assess function and usability of the two alternate algorithms in a highly supervised environment and provide an estimate of effect size and standard deviation in order to power future larger studies. During the study, we will challenge the performance of the two systems with different meal compositions and exercise.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 77350 0
Dr Martin de Bock
Address 77350 0
Department of Diabetes and Endocrinology
Princess Margaret Hospital
1 Roberts Road
Subiaco
Western Australia 6008
Country 77350 0
Australia
Phone 77350 0
+61 8 93408090
Fax 77350 0
Email 77350 0
[email protected]
Contact person for public queries
Name 77351 0
Dr Martin de Bock
Address 77351 0
Department of Diabetes and Endocrinology
Princess Margaret Hospital
1 Roberts Road
Subiaco
Western Australia 6008
Country 77351 0
Australia
Phone 77351 0
+61 8 93408090
Fax 77351 0
Email 77351 0
[email protected]
Contact person for scientific queries
Name 77352 0
Dr Martin de Bock
Address 77352 0
Department of Diabetes and Endocrinology
Princess Margaret Hospital
1 Roberts Road
Subiaco
Western Australia 6008
Country 77352 0
Australia
Phone 77352 0
+61 8 93408090
Fax 77352 0
Email 77352 0
[email protected]

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