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Trial registered on ANZCTR


Registration number
ACTRN12623000623695p
Ethics application status
Submitted, not yet approved
Date submitted
24/05/2023
Date registered
7/06/2023
Date last updated
7/06/2023
Date data sharing statement initially provided
7/06/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
EVOLUTION trial (EValuating glucose contrOL Using a next generaTION automated insulin delivery algorithm in patients with type 1 and type 2 diabetes: EVOLUTION)
Scientific title
Evaluating glucose control using a next generation automated insulin delivery algorithm in patients with type 1 and type 2 diabetes
Secondary ID [1] 309730 0
None
Universal Trial Number (UTN)
U1111-1292-9658
Trial acronym
EVOLUTION
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes mellitus 330120 0
Type 2 diabetes mellitus 330121 0
Condition category
Condition code
Metabolic and Endocrine 327002 327002 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention is a next-generation automated insulin delivery (AID) system, which is a modification of the existing commercial Omnipod 5 AID system (Insulet corporation), using a modified version of the Omnipod 5 Pod, modified version of the Omnipod 5 controller, and the commercially available Dexcom G6 continuous glucose monitoring (CGM) system.

This is a single-arm study with 4 phases.

Phase 1: participants will use a blinded Dexcom G6 CGM for 2 weeks while continuing their usual diabetes therapy, to assess baseline glycaemic control.

Phase 2 (participants with type 1 diabetes only): participants will use the Omnipod 5 Pod and Dexcom G6 CGM as sensor-augmented pump therapy in an outpatient setting, for 48 hours. During this time the Pod will be controlled manually by participants. Basal insulin delivery rates will be programmed by study staff based on review of prior insulin delivery and glucose levels. Participants will be instructed to deliver manual meal and correction insulin doses as per their usual routine.

Phase 3 (participants with type 1 diabetes only): immediately after completion of phase 2, participants will complete a 3 day/2 night supervised hotel stay using the investigational AID system while also participating in meal and exercise challenges at a defined target glucose setting of 5.6 mmol/L. On arrival at the hotel participants will continue to use their active Dexcom G6 CGM sensor and will activate a new Pod. During the first 24 hours participants will be instructed to not bolus for meals. For the following 24 hours, participants will be instructed to bolus for meals. Study staff will document all meals including snacks and describe what the meal consisted of, including the number of grams of carbohydrates. When mealtime boluses are to be delivered these will be determined using a bolus calculator with the calculated carbohydrate content of each meal. At least 2 meals each day must contain at least 60 grams of carbohydrate.

During phase 3 participants will take part in 45 minutes of supervised exercise each day. Participants will be free to choose a type of exercise, which of moderate intensity as per CDC guidelines (https://www.cdc.gov/physicalactivity/basics/adults/index.htm).

Phase 4 will only occur if data obtained from phase 3 meet pre-specified criteria. If these criteria are not met then the investigational AID system may be modified and phase 3 repeated. The details of phase 4 are described in a separate trial registration.

The pre-specified criteria are listed below. Evaluation for these criteria require a minimum of 10 participants with type 1 diabetes to complete phase 3 with a minimum of 48 hours use of AID during this phase.
1. No severe hypoglycaemia or diabetic ketoacidosis related to the AID system.
2. No unanticipated adverse device effects (UADE).
3. Average percentage of time that CGM-detected glucose is < 3.0 mmol/L is < 1%
4. Average percentage of time that CGM-detected glucose is < 3.9 mmol/L is < 4%
5. Average percentage of time that CGM-detected glucose is > 13.9 mmol/L is < 25%
6. Average hypoglycaemia treatments < 2/person/day for CGM-detected glucose < 3.9 mmol/L, excluding exercise-induced hypoglycaemia; multiple treatments for the same event are counted as one until CGM > 3.9 mmol/L for 30 minutes

Participants with type 1 diabetes will complete phases 1, 2, and 3 in immediate succession (i.e. phase 2 commences immediately after phase 1, phase 3 commences immediately after phase 2). Participants with type 2 diabetes will complete phase 1 but not phase 2 or 3.
Intervention code [1] 326169 0
Treatment: Devices
Intervention code [2] 326170 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334860 0
Percentage of time that glucose is <3.9 mmol/L as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [1] 334860 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Primary outcome [2] 334861 0
Percentage of time that glucose is >13.9 mmol/L as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [2] 334861 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [1] 422264 0
Mean glucose, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [1] 422264 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [2] 422265 0
Percentage of time that glucose is < 3.0 mmol/L, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [2] 422265 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [3] 422266 0
Percentage of time that glucose is > 10.0 mmol/L, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [3] 422266 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy..
Secondary outcome [4] 422267 0
Percentage of time that glucose is > 16.7 mmol/L, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [4] 422267 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [5] 422268 0
Percentage of time that glucose is between 3.9-10.0 mmol/L, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [5] 422268 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [6] 422269 0
Standard deviation of glucose values, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [6] 422269 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.
Secondary outcome [7] 422270 0
Average total daily insulin dose delivered by Omnipod 5 Pod as determined by Pod insulin delivery records, expressed as dose in units and weight-adjusted dose (dose in units divided by participant weight in kilograms)
Timepoint [7] 422270 0
Throughout duration of phase 3 (3 days/2 nights). Further stratified by recommended bolus therapy.
Secondary outcome [8] 422271 0
Average number of manual insulin boluses delivered by participant per day as determined by Omnipod 5 Pod insulin delivery records
Timepoint [8] 422271 0
Throughout duration of phase 3 (3 days/2 nights). Further stratified by recommended bolus therapy.
Secondary outcome [9] 422272 0
Average number of hypoglycaemia treatments per person per day, given for glucose < 3.9 mmol/L as measured by continuous glucose monitor, excluding exercise-induced hypoglycaemia. Multiple treatments for the same event are counted as one treatment until glucose is > 3.9 mmol/L for 30 minutes, as measured by continuous glucose monitor.
Timepoint [9] 422272 0
Phase 3: over the 3 day/2 night period
Secondary outcome [10] 422459 0
Average dose of insulin delivered by manual insulin boluses per participant per day as determined by Omnipod 5 Pod insulin delivery records
Timepoint [10] 422459 0
Throughout duration of phase 3 (3 days / 2 nights), further stratified by recommended bolus therapy
Secondary outcome [11] 422666 0
Coefficient of variation of glucose values, as measured by continuous glucose monitor and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [11] 422666 0
Continuous glucose monitoring throughout duration of phase 3 (3 days/2 nights), as compared to phase 1 (2 weeks). Further stratified by recommended bolus therapy.

Eligibility
Key inclusion criteria
1. Age at time of consent 16+ years
2. Individuals must be diagnosed with type 1 diabetes based on investigator’s clinical judgment for at least 1 year. Individuals diagnosed with type 2 diabetes must be on basal and bolus insulin therapy, with no specified duration.
3. A1C between 7.5-11.0% at screening
4. Currently using U-100 rapid-acting insulin analogs with insulin pump or receiving multiple daily injections suitable for conversion to pump therapy for at least 3 months prior to study start
5. Willing to use a Dexcom G6 CGM for the duration of the study
6. Willing to use the Omnipod® 5 Automated Insulin Delivery System during the study
7. Willing to perform all fingerstick BG testing with their personal blood glucose meter at the frequency specified in the study protocol or per investigator discretion
8. Willing to participate in at least 45 minutes of exercise and meal challenges during the 3 day hotel stay (participants with type 1 diabetes only)
9. Willing to use carbohydrate counting for determination of meal boluses
10. Willing and able to sign the Informed Consent Form (ICF) and/or has a parent/guardian willing and able to sign the ICF.
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Any medical condition, such as untreated malignancy, unstable cardiac disease, unstable or end-stage renal failure, eating disorders, or other conditions which in the opinion of the investigator, would put the participant at an unacceptable safety risk
2. Blood disorder or dyscrasia within 3 months prior to screening, including the use of hydroxyurea, which in the investigator’s opinion could interfere with determination of HbA1C.
3. History of severe hypoglycemia within the past 6 months
4. History of diabetic ketoacidosis or hyperglycemic hyperosmolar syndrome in the past 6 months, unrelated to an intercurrent illness or infusion set failure
5. History of moderate to severe preproliferative or proliferative retinopathy based on screening within the last 12 months.
6. Planning to start a non-insulin anti-diabetic medication during the study. If on non-insulin medication, dose must be stable in the previous 30 days.
7. Planning to start a weight-loss agent during the study. If on a weight-loss medication, dose must be stable in the previous 30 days.
8. Currently on a low carbohydrate diet of < 60 grams of carbohydrates per day
9. Pregnant, or is a woman of childbearing potential and not on acceptable form of birth control (acceptable forms of contraception include abstinence, barrier methods such as condoms, hormonal contraceptives, intrauterine device, surgical sterilisation such as tubal ligation or hysterectomy, or vasectomised partner)
10. Dermatological conditions at the proposed sensor/pump wear sites that in the investigator’s opinion could preclude ability to wear the Pod and/or the Dexcom sensor
11. Current or known history of coronary artery disease that is not stable with medical management, including unstable angina, or angina that prevents moderate exercise despite medical management, or a history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting within the previous 12 months.
12. Currently on systemic steroids or intends to receive systemic steroid treatment in the next 6 months, including stable treatment for adrenal insufficiency. Inhaled, ophthalmic, topical, joint injection, and other locally applied steroids are allowed.
13. Currently participating in another clinical study using an investigational drug or device
14. Recent (within the preceding 30 days) participation in a clinical study using an investigational drug
15. Unable to follow the clinical protocol for the duration of the study or is otherwise deemed unacceptable to participate in the study per the investigator’s clinical judgment

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)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
As this is a first-in-human feasibility study, outcomes are exploratory and descriptive. Continuous variables will be summarised using descriptive statistics, including counts, mean, median, standard deviation, minimum and maximum. Where appropriate, first and third quartile will be presented. If the observed data are found not to follow a normal distribution, appropriate non-parametric methods may be employed. There are no hypotheses associated with the primary or secondary endpoints.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/07/2023
Actual
Date of last participant enrolment
Anticipated
1/10/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 25553 0
New Zealand
State/province [1] 25553 0

Funding & Sponsors
Funding source category [1] 313920 0
Commercial sector/Industry
Name [1] 313920 0
Insulet Corporation
Country [1] 313920 0
United States of America
Primary sponsor type
University
Name
University of Otago
Address
362 Leith Street
Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 315782 0
None
Name [1] 315782 0
Address [1] 315782 0
Country [1] 315782 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313066 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 313066 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 313066 0
New Zealand
Date submitted for ethics approval [1] 313066 0
23/05/2023
Approval date [1] 313066 0
Ethics approval number [1] 313066 0

Summary
Brief summary
Automated insulin delivery (AID; also known as closed loop or artificial pancreas) is an emerging therapy that improves outcomes for people with diabetes. This study investigates a "next-generation" AID system.

The study will include at least 24 adults, of whom 12 will have type 1 diabetes and 12 will have type 2 diabetes.

For the first two weeks of the study all participants will continue with their usual diabetes treatment while wearing a blinded continuous glucose monitor.

Participants with type 1 diabetes will then use the next-generation AID system in a controlled environment. Following 48 hours of home use of the insulin pump and unblinded continuous glucose monitor in manual mode, they will complete a 3 day / 2 night hotel stay, under the supervision of research staff. During the hotel stay they will use the next-generation AID system and undergo pre-defined meal and exercise challenges. At the end of the hotel stay, glucose data will be evaluated to see if it meets pre-specified criteria to indicate satisfactory AID system performance. If these criteria are not met then the AID system may be modified and the hotel stay repeated, either with the same participants or with a group of new participants.

If the data from the hotel study meet the pre-specified criteria, then all participants (type 1 and type 2 diabetes) will proceed to home use of the next-generation AID system. This is further described in a separately registered trial, specifically covering the home AID phase.

Glucose and pump data will be collected throughout the study to assess the performance of the next-generation AID system at various time points.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 126870 0
A/Prof Martin de Bock
Address 126870 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 126870 0
New Zealand
Phone 126870 0
+64 21 195 6579
Fax 126870 0
Email 126870 0
martin.debock@otago.ac.nz
Contact person for public queries
Name 126871 0
A/Prof Martin de Bock
Address 126871 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 126871 0
New Zealand
Phone 126871 0
+64 21 195 6579
Fax 126871 0
Email 126871 0
martin.debock@otago.ac.nz
Contact person for scientific queries
Name 126872 0
A/Prof Martin de Bock
Address 126872 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 126872 0
New Zealand
Phone 126872 0
+64 21 195 6579
Fax 126872 0
Email 126872 0
martin.debock@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Privacy laws in New Zealand


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.