Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623000634673p
Ethics application status
Submitted, not yet approved
Date submitted
30/05/2023
Date registered
13/06/2023
Date last updated
13/06/2023
Date data sharing statement initially provided
13/06/2023
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): Phase 4
Scientific title
Evaluating glucose control using a next generation automated insulin delivery algorithm in patients with type 1 and type 2 diabetes: Phase 4
Secondary ID [1] 309789 0
None
Universal Trial Number (UTN)
U1111-1292-9658
Trial acronym
EVOLUTION
Linked study record
The current study is a follow-on study to ACTRN12623000623695 (EVOLUTION trial Phases 1-3)

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes mellitus 330197 0
Type 2 diabetes mellitus 330198 0
Condition category
Condition code
Metabolic and Endocrine 327070 327070 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. Compared to the existing Omnipod 5 system, the next-generation system aims to improve the algorithm response to hyperglycaemia while still maintaining the desired safety profile with regard to hypoglycaemia. Multiple changes have been made to the algorithm accordingly, including allowing the algorithm to operate at a target as low as 5.6 mmol/L, rather than the minimum target of 6.1 mmol/L available in Omnipod 5.

This is a single-arm study with 4 phases. Phases 1-3 are described in a separate ANZCTR trial registration (AZTRN12623000623695). Phase 4 will only occur if data from phase 3 meet pre-specified criteria (described in the phase 3 trial registration).

During phase 4, participants will use the next generation AID system in their usual home environment for 6 weeks. During weeks 1-3 participants will be asked to give manual insulin boluses for meals using the Omnipod 5 Pod in accordance with their usual diabetes treatment routine. During weeks 4-6 participants will be instructed to not bolus for meals, however manual correction boluses should still be given if CGM-detected glucose is >16.7 mmol/L for >one hour.

Participants will attend at least 3 in-person study visits during phase 4. At the first visit, participants who have not previously used the AID system will receive training in its use, including training in how to self-insert and replace the study devices. The study team will additionally conduct electronic remote review of glucose values and pump delivery records at least weekly, and make contact with participants as needed. This remote review will also be used to monitor adherence to the intervention.

For participants with type 1 diabetes, phase 4 may commence immediately after the conclusion of phase 3 (if the pre-specified acceptance criteria are met), or there may be an intervening period between phase 3 and 4 during which participants use their normal diabetes therapy.

Participants with type 2 diabetes will not complete phases 2 and 3 of the trial. These participants may commence phase 4 immediately after completing phase 1, or there may be an intervening period between phase 1 and 4 during which participants use their normal diabetes therapy.
Intervention code [1] 326218 0
Treatment: Devices
Intervention code [2] 326219 0
Treatment: Other
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 334924 0
Percentage of time that glucose is <3.9 mmol/L as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [1] 334924 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Primary outcome [2] 334925 0
Percentage of time that glucose is >13.9 mmol/L as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [2] 334925 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [1] 422460 0
Mean glucose, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [1] 422460 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [2] 422461 0
Percentage of time that glucose is < 3.0 mmol/L, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [2] 422461 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [3] 422462 0
Percentage of time that glucose is > 10.0 mmol/L, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [3] 422462 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [4] 422463 0
Percentage of time that glucose is > 16.7 mmol/L, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [4] 422463 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [5] 422464 0
Percentage of time that glucose is between 3.9-10.0 mmol/L, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [5] 422464 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [6] 422465 0
Standard deviation of glucose values, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [6] 422465 0
Continuous glucose monitoring throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [7] 422466 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), reported separately for participants with type 1 and type 2 diabetes
Timepoint [7] 422466 0
Throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [8] 422467 0
Average number of manual insulin boluses delivered by participant per day as determined by Omnipod 5 Pod insulin delivery records, reported separately for participants with type 1 and type 2 diabetes
Timepoint [8] 422467 0
Throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [9] 422468 0
Average dose of insulin delivered by manual insulin boluses per participant per day as determined by Omnipod 5 Pod insulin delivery records, reported separately for participants with type 1 and type 2 diabetes
Timepoint [9] 422468 0
Throughout six-week duration of phase 4. Further stratified by recommended bolus therapy.
Secondary outcome [10] 422669 0
Coefficient of variation of glucose values, as measured by continuous glucose monitor, reported separately for participants with type 1 and type 2 diabetes, and further stratified as daytime (0600-2359hrs) or nighttime (0000-0559hrs).
Timepoint [10] 422669 0
Continuous glucose monitoring throughout six-week duration of phase 4. 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 use carbohydrate counting for determination of meal boluses
9. 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
17/11/2023
Actual
Date of last data collection
Anticipated
31/12/2023
Actual
Sample size
Target
24
Accrual to date
Final
Recruitment outside Australia
Country [1] 25560 0
New Zealand
State/province [1] 25560 0

Funding & Sponsors
Funding source category [1] 313971 0
Commercial sector/Industry
Name [1] 313971 0
Insulet Corporation
Country [1] 313971 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] 315844 0
None
Name [1] 315844 0
Address [1] 315844 0
Country [1] 315844 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 313106 0
Northern B Health and Disability Ethics Committees
Ethics committee address [1] 313106 0
Health and Disability Ethics Committees
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington 6011
Ethics committee country [1] 313106 0
New Zealand
Date submitted for ethics approval [1] 313106 0
23/05/2023
Approval date [1] 313106 0
Ethics approval number [1] 313106 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 24 adults, of whom 12 will have type 1 diabetes and 12 will have type 2 diabetes.

Prior to this study, the next-generation AID system will have been assessed in at least 10 participants with type 1 diabetes in a controlled hotel environment. This study will only proceed if data from that hotel assessment meet pre-specified criteria indicating that the AID system is safe to trial in a home setting.

Participants will use the next-generation AID system in their home setting for six weeks, following their usual day-to-day routines. During the first three weeks they will give themselves manual insulin doses before all planned meals. During the second three weeks they will stop routinely giving manual insulin doses before meals.

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

Contacts
Principal investigator
Name 127026 0
A/Prof Martin de Bock
Address 127026 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 127026 0
New Zealand
Phone 127026 0
+64 21 195 6579
Fax 127026 0
Email 127026 0
martin.debock@otago.ac.nz
Contact person for public queries
Name 127027 0
A/Prof Martin de Bock
Address 127027 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 127027 0
New Zealand
Phone 127027 0
+64 21 195 6579
Fax 127027 0
Email 127027 0
martin.debock@otago.ac.nz
Contact person for scientific queries
Name 127028 0
A/Prof Martin de Bock
Address 127028 0
University of Otago
Terrace House, 4 Oxford Terrace
Christchurch 8011
Country 127028 0
New Zealand
Phone 127028 0
+64 21 195 6579
Fax 127028 0
Email 127028 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.