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Trial registered on ANZCTR


Registration number
ACTRN12618000840280
Ethics application status
Approved
Date submitted
14/05/2018
Date registered
18/05/2018
Date last updated
30/04/2019
Date data sharing statement initially provided
30/04/2019
Date results information initially provided
30/04/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Glucose control using an advanced hybrid closed-loop system
Scientific title
Glucose time-in-target range using an advanced hybrid closed-loop system in adults with type 1 diabetes
Secondary ID [1] 294866 0
None
Universal Trial Number (UTN)
U1111-1213-9370
Trial acronym
CAMP 2.0
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 307817 0
Condition category
Condition code
Metabolic and Endocrine 306864 306864 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This will be a prospective, three-stage study involving 12 pump-experienced adults with type 1 diabetes. Following a 1-week period of run-in, the first stage will take place in a supervised ‘in-hotel’ setting (5 days), followed by a second stage supervised ‘in-hospital’ (1 day) and finally a third stage in a ‘free living’ setting at home (3 weeks). Participants will be assigned the study insulin pump for a period of approximately 5 weeks.

The hybrid closed-loop (HCL) insulin delivery system incorporates a proportional-integral derivative (PID) control algorithm with insulin feedback. The HCL system comprises a glucose sensor 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 delivered every 5 minutes to account for basal insulin requirements. Participant-initiated bolus insulin doses are still required for meals. HCL systems have been shown to be safe and effective in improving glucose control. Based upon prior experience, modifications have been made to previous iterations of the HCL system to develop an advanced-HCL system to be used as the study pump. The main modifications to the study pump include: 1) correction boluses using sensor glucose and commands by the algorithm without the need for user confirmation; 2) the ability to make therapeutic insulin dosing decisions using the sensor glucose without the need for finger-prick glucose values; 3) a more aggressive algorithm aiming to improve time-in-target glucose range.

All participants will use the study pump for the study duration. Education specific to the study pump will be provided face-to-face by an experienced study doctor and diabetes nurse educator, and will be tailored to each participants’ prior knowledge. Participants will also be provided educational material and resources, including a user guide booklet for the study pump.

Stage 1 – ‘In-Hotel’: Participants will live in a supervised environment for 5 days using the study pump with a study doctor and nurse present at all times. Participants’ glucose levels will be monitored remotely at all times by the study team. Three interventions will be implemented during this time including: 1) Missed meal bolus (insulin bolus unannounced) on Day 3; 2) Late meal bolus (insulin bolus will be administered 20 minutes after the meal was commenced) on Day 4; 3) Moderate intensity exercise (2 hour walk) on Day 5. All food will be provided from a standard menu with a variety of vegetarian, non-vegetarian and gluten-free meals from which participants will be able to freely choose their meals.

Stage 2 – ‘In-Hospital’: Sensor miscalibration will occur in a hospital supervised setting over a 24-hour period. There will be three study doctors, four study nurses and a scientist present for this period. Participants will be randomised to either over-calibrate or under-calibrate the sensor by 40% of their true glucose value. The CL function will be turned off during this miscalibration period. Participants will continue to over or under-calibrate their sensor every 3 hours for a total of 12 hours. For safety purposes, all participants will wear a second glucose sensor which will be calibrated with their true glucose values. Following 12 hours of sensor miscalibration, the CL function will be re-activated. Frequent blood sampling will be conducted overnight using iSTAT (Abbott Point of Care, Princeton, NJ) or YSI for venous glucose levels at 30 minute intervals for 12 hours. Shorter time interval blood sampling will occur if glucose levels are <4.4mmol/L. Hypoglycaemia will be treated with usual clinical care. The frequent sampling will finish at ~8.00am the following morning.

Stage 3 - Free-Living ‘At-home’: Participants will enter this stage if there have been no episodes of severe hypoglycaemia or ketoacidosis during the supervised stage of the study. If eligible to return home using the study pump, participants will be discharged home to undertake their usual activities of daily living. They will be required to upload their insulin pumps twice-weekly for review by a study doctor. After three weeks at home, they will return for their end-of-study visit and all study devices will be returned. A user-evaluation questionnaire will be completed. Participants will recommence management using their own insulin pumps with pre-existing settings.
Intervention code [1] 301175 0
Treatment: Devices
Intervention code [2] 301176 0
Treatment: Drugs
Comparator / control treatment
N/A
Control group
Uncontrolled

Outcomes
Primary outcome [1] 305853 0
Total % continuous glucose monitoring (CGM) time spent within target glucose range (3.9–10mmol/L) using CGM data uploaded from the MiniMed Medtronic device
Timepoint [1] 305853 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
Secondary outcome [1] 346778 0
CGM % time spent >10.0 mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [1] 346778 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [2] 346779 0
CGM % time spent in 3.9-7.8mmol/L range using CGM data uploaded from the MiniMed Medtronic device
Timepoint [2] 346779 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [3] 346780 0
CGM % time >13.9mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [3] 346780 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [4] 346781 0
CGM % time >16.7mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [4] 346781 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [5] 346782 0
CGM area under curve (AUC) > 10mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [5] 346782 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [6] 346783 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] 346783 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [7] 346784 0
CGM % time spent <3.9mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [7] 346784 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [8] 346785 0
CGM % time spent <3.3mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [8] 346785 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [9] 346786 0
CGM % time spent <2.8mmol/L using CGM data uploaded from the MiniMed Medtronic device
Timepoint [9] 346786 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [10] 346787 0
Major hypoglycaemic episodes (n) defined as requiring third party assistance (self-reported or observed episodes)
Timepoint [10] 346787 0
Cumulative total of this outcome (n) will be analysed throughout each study period.
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [11] 346788 0
Episodes of ketosis (n) defined as a blood ketone level > 0.6mmol/L on finger-prick ketone testing
Timepoint [11] 346788 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) will be analysed throughout each study period.
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [12] 346789 0
Episodes of ketoacidosis (n) measured using finger-prick ketone testing and blood gas analysis in hospital
Timepoint [12] 346789 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.
During and 4 hours post-interventions eg. late meal-bolus; missed meal-bolus; exercise; sensor miscalibration (specific to a particular intervention and aggregated)
Secondary outcome [13] 346790 0
Unscheduled exits from CL (n) using CGM data uploaded from the MiniMed Medtronic device
Timepoint [13] 346790 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
Secondary outcome [14] 346791 0
Time (%) in CL using CGM data uploaded from the MiniMed Medtronic device
Timepoint [14] 346791 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
Secondary outcome [15] 346792 0
Total insulin delivery (units) using CGM data uploaded from the MiniMed Medtronic device
Timepoint [15] 346792 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])
Secondary outcome [16] 346793 0
Sensor mean absolute relative difference (MARD) with glucose meter as a reference using CGM data uploaded from the MiniMed Medtronic device
Timepoint [16] 346793 0
Measured for 4 weeks (Stage 1 – 3 of the study [ie. Week 2, 3, 4, 5])

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

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)
N/A
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)
Safety/efficacy
Statistical methods / analysis
This represents an exploratory trial to provide preliminary data on the advanced-HCL system. Available data does not allow a power calculation to be performed. As the protocol does not include a comparator, a descriptive analysis only will be undertaken. Analysis will be performed for each of the three stages independently.

Recruitment
Recruitment status
Completed
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] 10881 0
St Vincent's Hospital (Melbourne) Ltd - Fitzroy
Recruitment postcode(s) [1] 22639 0
3065 - Fitzroy

Funding & Sponsors
Funding source category [1] 299453 0
Hospital
Name [1] 299453 0
St Vincent's Hospital Melbourne
Address [1] 299453 0
41 Victoria Pde
Fitzroy VIC 3065
Country [1] 299453 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] 298750 0
None
Name [1] 298750 0
Address [1] 298750 0
Country [1] 298750 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300359 0
St Vincent's Hospital Melbourne
Ethics committee address [1] 300359 0
Research Governance Unit
27 Victoria Pde
Fitzroy VIC 3065
Ethics committee country [1] 300359 0
Australia
Date submitted for ethics approval [1] 300359 0
02/04/2018
Approval date [1] 300359 0
18/04/2018
Ethics approval number [1] 300359 0
HREC 074/18

Summary
Brief summary
BACKGROUND: The ‘artificial pancreas’ or hybrid closed-loop (HCL) insulin pump has been shown to be effective in improving glucose control in individuals with type 1 diabetes. The HCL system has been further modified from previous prototypes resulting in the advanced-HCL (A-HCL) system. The A-HCL system aims to increase time-in-target glucose range and improve user acceptability. The impact of the modifications implemented in A-HCL systems have yet to be evaluated.

AIMS: The study aims to generate preliminary data regarding glucose control using A-HCL systems, and challenged by meal interventions, exercise and sensor miscalibrations.

METHODS: The study is a prospective, three-stage study, incorporating ‘in-hotel’, ‘in-hospital’ and ‘free-living’ stages over a 5 week duration. Pump-experienced adults with type 1 diabetes will be recruited. All participants will be assigned the A-HCL system. Interventions in the supervised ‘in-hotel’ and ‘in-hospital’ stage aim to challenge glucose control and A-HCL system performance. Thereafter, participants will return home in the ‘free-living’ stage for 3 weeks using the A-HCL system.

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 83394 0
Prof David O'Neal
Address 83394 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 83394 0
Australia
Phone 83394 0
+61 3 9231 2211
Fax 83394 0
Email 83394 0
dno@unimelb.edu.au
Contact person for public queries
Name 83395 0
Dr Melissa Lee
Address 83395 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 83395 0
Australia
Phone 83395 0
+61 3 9231 2211
Fax 83395 0
Email 83395 0
melissa.lee@svha.org.au
Contact person for scientific queries
Name 83396 0
Dr Melissa Lee
Address 83396 0
St Vincent's Hospital Melbourne
41 Victoria Pde Fitzroy VIC 3065
Country 83396 0
Australia
Phone 83396 0
+61 3 9231 2211
Fax 83396 0
Email 83396 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