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Trial registered on ANZCTR


Registration number
ACTRN12617001449325
Ethics application status
Approved
Date submitted
6/10/2017
Date registered
12/10/2017
Date last updated
12/10/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Glucose control during hybrid closed loop using an enhanced vs standard algorithm in adults with type 1 diabetes in a supervised hotel setting
Scientific title
Glucose control during hybrid closed loop using an enhanced vs standard ePID algorithm with insulin feedback in adults with type 1 diabetes: a randomised crossover study
Secondary ID [1] 293076 0
None
Universal Trial Number (UTN)
U1111-1203-2469
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes
 305007 0
Condition category
Condition code
Metabolic and Endocrine 304328 304328 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be assigned the Minimed Medtronic 670G system version 3.1 and the Minimed Medtronic 670G 3.0 closed loop systems in random order for a period of 7- days each, with stages separated by 1 week.

The study is a two-stage randomized crossover study in a supervised live-in setting (hotel facility) performed in pump-experienced adults with type 1 diabetes.

The MiniMed™ 670G system (Medtronic, Northridge, CA) includes the features of a conventional sensor augmented insulin pump, and also incorporates a PID control algorithm with the addition of insulin feedback plus limits on the maximum rate of insulin delivery and duration of insulin suspension. This control algorithm automatically determines the insulin dose based on information from the continuous glucose monitor (Enlite 3 sensor and GST3 Minilink transmitter) every 5 minutes, and calculates the insulin dose to maintain the individual within target glucose range. Based upon prior experience modifications have been made to the current iteration of the control algorithm (Version 3.0) resulting in Version 3.1 that aims to improve hyperglycaemia correction and time spent in automode. The system includes two external devices - an insulin pump and a continuous glucose monitor. The insulin pump can sit anywhere on the body and is connected to a subcutaneous cannula via plastic tubing (an infusion set). The cannula is generally inserted in the subcutaneous tissue on the abdomen or the buttock. The continuous glucose monitor is generally worn on the abdomen but can be worn anywhere there is an adequate amount of subcutaneous tissue. It sits on the skin above the inserted subcutaneous sensor.

Participants will be required to perform at least 3 fingerpick glucose levels per day for sensor calibration using the Contour Next Link 2.4 blood glucose meter. Glucose data will be collected for each entire study week. Participants will also undergo 4 challenges to the closed loop system (each one performed on a separate day) , these including a missed bolus insulin dose (or unannounced meal), a high fat meal containing 40g of fat, a high GI meal (glycemic index ~70, glycemic load ~45) and a 40 minute bout of high intensity interval exercise (including five minutes of warm-up, then six repetitions of 4 minutes of exercise at high intensity (75% of age-predicted maximal heart rate) followed by 2 minutes of complete rest, an additional 4 minutes rest will be provided between the third and fourth repetitions).

Data on intervention adherence defined as time in closed loop (automode) will be available via device upload and will be analysed. There will be no specific strategies used to maintain or improve fidelity other than device training and education prior to the study weeks.
Intervention code [1] 299318 0
Treatment: Devices
Comparator / control treatment
The comparator is the Minimed Medtronic 670G version 3.0 closed loop system. As this is a cross-over trial, all participants will receive both Minimed Medtronic 670G version 3.0 and the Minimed Medtronic 670G version 3.1 closed loop system.
Control group
Active

Outcomes
Primary outcome [1] 303590 0
Total % CGM time spent within target glucose range (3.9–10mmol/L)
using CGM data uploaded from the Minimed Medtronic device
Timepoint [1] 303590 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
Secondary outcome [1] 339522 0
CGM % time spent >10.0 mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [1] 339522 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [2] 339523 0
CGM % time spent in 3.9--7.8mmol/L range
using CGM data uploaded from the Minimed Medtronic device
Timepoint [2] 339523 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [3] 339524 0
CGM % time >13.9mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [3] 339524 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [4] 339625 0
CGM % time >16.7mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [4] 339625 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [5] 339626 0
CGM AUC > 10mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [5] 339626 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [6] 339627 0
Glycaemia variability as determined by mean amplitude of glycaemic excursions (MAGE) and standard deviation (SD)
using CGM data uploaded from the Minimed Medtronic device
Timepoint [6] 339627 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [7] 339628 0
CGM% time spent <3.9mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [7] 339628 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [8] 339629 0
CGM % time spent <3.3mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [8] 339629 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [9] 339630 0
CGM % time spent <2.8mmol/L
using CGM data uploaded from the Minimed Medtronic device
Timepoint [9] 339630 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [10] 339631 0
Major hypoglycaemic episodes (n) defined as requiring third party assistance as documented by study staff
Timepoint [10] 339631 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [11] 339632 0
Episodes of ketosis (n) defined as a blood ketone level > 0.6mmol/L on fingerprick ketone testing
Timepoint [11] 339632 0
Finger-prick ketone levels will be done only if BGL>14 on continuous glucose monitoring or if clinically indicated (i.e. participant unwell)
Cumulative total of this outcome (n) with be analysed throughout each 1 week study arm (week 2 and 4 post randomisation). During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [12] 339633 0
Episodes of ketoacidosis (n) measured using blood gas analysis in hospital
Timepoint [12] 339633 0
This will only occur if the participant becomes unwell, is ketotic on finger-prick ketone testing and admission to hospital is clinical indicated.
Cumulative total of this outcome (n) with be analysed throughout each 1 week study arm (week 2 and 4 post randomisation). During and 4 hours post-interventions eg. high GI meal; high fat meal; missed meal-bolus; and exercise (specific to a particular intervention and aggregated)
Secondary outcome [13] 339634 0
Unscheduled exits from CL (n)
using CGM data uploaded from the Minimed Medtronic device
Timepoint [13] 339634 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
Secondary outcome [14] 339635 0
Time (%) in CL
using CGM data uploaded from the Minimed Medtronic device
Timepoint [14] 339635 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
Secondary outcome [15] 339636 0
Total insulin delivery (Units)
using CGM data uploaded from the Minimed Medtronic device
Timepoint [15] 339636 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)
Secondary outcome [16] 339637 0
Sensor MARD with glucose meter as a reference
using CGM data uploaded from the Minimed Medtronic device
Timepoint [16] 339637 0
Throughout each 1 week study arm (week 2 and 4 post randomisation)

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<40
History of diabetic ketoacidosis in the last 3 months
Diabetic gastroparesis
Unable to exercise

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
Crossover
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This represents an exploratory trial and available data does not allow a power calculation to be performed. Statistical comparisons will be between CL 670G 3.0 and 670G 3.1 for primary and secondary endpoints. Additional analyses will be performed specific to interventions eg high GI meals, exercise, insulin delivery suspension etc. Data will be analysed using ANCOVA. If the outcome cannot be normalised or if the ANCOVA model is of poor fit, non-parametric analysis will be performed (Rank sum test). Qualitative data obtained will be subjected to a descriptive analysis.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
12/10/2017
Actual
Date of last participant enrolment
Anticipated
16/10/2017
Actual
Date of last data collection
Anticipated
16/11/2017
Actual
Sample size
Target
12
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9164 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 17677 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 297698 0
Hospital
Name [1] 297698 0
St Vincent's Hospital
Country [1] 297698 0
Australia
Primary sponsor type
Hospital
Name
St Vincent's Hospital Melbourne
Address
41 Victoria Pde
Fitzroy VIC 3065
Country
Australia
Secondary sponsor category [1] 296729 0
None
Name [1] 296729 0
Address [1] 296729 0
Country [1] 296729 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298769 0
St Vincent's Hospital Melbourne
Ethics committee address [1] 298769 0
Research Governance Unit
27 Victoria Pde
Fitzroy VIC 3065
Ethics committee country [1] 298769 0
Australia
Date submitted for ethics approval [1] 298769 0
01/09/2017
Approval date [1] 298769 0
28/09/2017
Ethics approval number [1] 298769 0
HREC176/17

Summary
Brief summary
BACKGROUND: The hybrid artificial pancreas or hybrid closed loop insulin pump (HCL) has been shown to be effective in improving glycaemia in individuals with type 1 diabetes (T1DM). Recently the Medtronic e-PID HCL algorithm with insulin feedback (670G 3.0 HCL system) has been modified (670G 3.1 HCL system) to enhance its effectiveness manage blood glucose levels. The impact of the modifications implemented in 670G 3.1 have yet to be demonstrated.
AIMS: The study aims to compare the relative effectiveness of the two HCL systems in managing blood glucose levels
METHODS: The study is a two-stage randomized crossover study in a supervised live in setting. Pump-experienced adults with type 1 diabetes will be recruited. Following a 1 week run-in, all participants will be assigned 670G 3.1 and 670G 3.0 HCL systems in random order for a period of 7 days each, with stages separated by 1 week. Interventions aimed at challenging glycaemic control hyperglycaemia will be implemented during each of the 7 days.
OUTCOME MEASURES: Glucose control including CGM time in target glucose range and time in hyperglycaemic and hypoglycaemic ranges. Safety end points including number of episodes of hypoglycaemia and ketoacidosis, and system performance
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78174 0
A/Prof David O'Neal
Address 78174 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 78174 0
Australia
Phone 78174 0
+61 3 9231 2211
Fax 78174 0
Email 78174 0
[email protected]
Contact person for public queries
Name 78175 0
Barbora Paldus
Address 78175 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 78175 0
Australia
Phone 78175 0
+61 3 9231 2211
Fax 78175 0
Email 78175 0
[email protected]
Contact person for scientific queries
Name 78176 0
Barbora Paldus
Address 78176 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 78176 0
Australia
Phone 78176 0
+61 3 9231 2211
Fax 78176 0
Email 78176 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes BARBORA PALDUS, MELISSA H. LEE, HANNAH JONES, SYBI... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseGlucose Control Using a Standard Versus an Enhanced Hybrid Closed Loop System: A Randomized Crossover Study.2019https://dx.doi.org/10.1089/dia.2018.0279
N.B. These documents automatically identified may not have been verified by the study sponsor.