Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000762459p
Ethics application status
Submitted, not yet approved
Date submitted
12/06/2025
Date registered
18/07/2025
Date last updated
18/07/2025
Date data sharing statement initially provided
18/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
The FLIP-IT trial - Fully automated artificial pancreas in adults with previously above-target type 1 diabetes
Scientific title
Closing the loop with the FLIP-IT trial – Efficacy and safety of fully automated insulin delivery and patch pumps in adults with type 1 diabetes and above-target glycaemia
Secondary ID [1] 314636 0
0001-FCL
Universal Trial Number (UTN)
U1111-1319-9154
Trial acronym
FLIP-IT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Type 1 diabetes 337786 0
Condition category
Condition code
Metabolic and Endocrine 334128 334128 0 0
Diabetes

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is an, open-label three-phase study. Expected duration of total participant study participation is 41 weeks (including 2 weeks of baseline data collection). Phase 1 is a two-group parallel 13-week randomized controlled trial (RCT) with participants randomized (on a 1:1 allocation) to either intervention or control. All participants will receive dietetic support with a focus from Day 43 on exploring the potential of nutrition therapy in optimization of fully automated insulin delivery (AID) without carbohydrate announcement. Phase 2 is a 13-week extension phase with different phased oral adjunctive therapy options given to all participants from Phase 1. Phase 3 is a two-group parallel 13-week RCT with participants not meeting pre-defined glycaemic targets (time in range [TIR] greater than 85% and time in tight range [TITR] greater than 60%) randomized (on a 1:1 allocation, stratified by phase 1 randomization) to either Tirzepatide, or continue current treatment.
Phase 1:
Following a 2-week baseline data collection period, participants (must be existing users of current AID therapy) will be allocated (on a 1:1 ratio) to 39 weeks of either: A: Medtrum TouchCare® Nano pump with associated open-source Android APS control algorithm (Patch-APS; Intervention arm); or B: Ongoing use of their traditional commercial AID therapy (Control arm).
At the start of the RCT, participants randomized to intervention group will receive face-to-face education at the study site by trained study staff with diabetes knowledge who are insulin pump education specialists based on the manufacturer's user guides. The initial educational session will take approximately 5-6 hours, including the device set-up. Participants’ pump data will be automatically uploaded to Cloud services (Nightscout or Tidepool) via Android APS App, which will be installed on participants’ phones. Pump settings will be refined by the study team by way of electronic review of the uploaded data. These refinements are personalized based on the participant’s uploaded data and will happen after each review of the uploaded pump data.
The first 6 weeks of Phase 1 will focus on optimization of therapy settings in both study arms. Then, participants in both study arms will receive additional support from a New Zealand Registered Dietitian in form of up to five sessions (approximately 1 hour each), following standard Nutritional Management of Diabetes guidelines, with a particular focus on carbohydrate quality to optimize fully automated insulin delivery without carbohydrate announcement. The primary focus will be to optimise each participant’s carbohydrate intake by prioritising quality sources like wholegrain and high fibre foods and limiting refined sugars.
Phase 2:
Following the 13-week RCT, both arms will commence a 13-week extension phase using their previously allocated AID system (Patch-APS or traditional AID) and commence oral medication (Metformin graded up for 6 weeks starting at 250mg once daily with largest meal, then increasing to 500mg BD in 250mg steps weekly [as tolerated], then addition of Vildagliptin for further 7 weeks).
Phase 3:
In this adaptive phase (following Phase 2), all participants not meeting the glycaemic targets of TIR =85% and TITR =65% in the previous 2 weeks will be allocated (on a 1:1 ratio, stratified by Phase 1 randomisation) to 13 weeks of either: A: Tirzepatide; or B: Continue Vildagliptin + Metformin.
Participants meeting the glycaemic targets will continue use of the treatment from Phase 2 for further 13 weeks.
Following the second randomisation, participants will receive one of four treatments: 1) Patch-APS and Tirzepatide; 2) Patch-APS and Vildagliptin+Metformin; 3) Traditional AID and Tirzepatide; or 4) Traditional AID and Vildagliptin+Metformin.
During the 13-week RCT phase, participants (regardless of study arm) will have system data review in-person/phone/virtual daily for the first week, twice weekly for 4 weeks, then weekly ending at 13-week visit. Intervention adherence will be assessed by way of review of device data uploaded to Cloud services as described above. During the 13-week extension phase using adjunctive oral medication, reviews will occur weekly while medication is titrated up and to check for complications/non-tolerance. Both arms will receive the same visit schedule. During the 13-week adaptive phase, participants will be contacted weekly for the first 4 weeks, and then monthly until the end of the study. Assessment of medication adherence will be done by way of direct participant questioning, review of prescription claims, and return of unused medication.
Intervention code [1] 331258 0
Treatment: Devices
Intervention code [2] 331259 0
Treatment: Drugs
Intervention code [3] 331260 0
Lifestyle
Comparator / control treatment
The control group will continue their usual diabetes therapy during the study (traditional commercial AID system). During Phase 2, the control group will receive the same oral medication as described for the intervention group. During the Adaptive Phase 3, control participants will continue use of the treatment from Phase 2. Participants randomized to the control group will receive the same personalized therapy review and support schedule as the intervention group during the study.
Control group
Active

Outcomes
Primary outcome [1] 341784 0
Glycaemic control as measured by percentage of time in range (3.9 – 10mmol/L).
Timepoint [1] 341784 0
At baseline, and at 6, 13 (primary timepoint), 26, and 39 weeks post-RCT commencement.
Secondary outcome [1] 448668 0
Glycaemic control as measured by percentage of time below 3.9 mmol/L.
Timepoint [1] 448668 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [2] 448669 0
Glycaemic control as measured by percentage of time below 3.0 mmol/L.
Timepoint [2] 448669 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [3] 448670 0
Glycaemic control as measured by percentage of time above 10.0 mmol/L.
Timepoint [3] 448670 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [4] 448671 0
Glycaemic control as measured by percentage of time above 13.9 mmol/L.
Timepoint [4] 448671 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [5] 448672 0
Glycaemic control as measured by percentage of time in range 3.9 to 7.8 mmol/L.
Timepoint [5] 448672 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [6] 448673 0
Glycaemic control as measured by coefficient of variation.
Timepoint [6] 448673 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [7] 448674 0
Glycaemic control as measured by proportion of participants meeting the glycaemic target of spending equal to or greater than 70% of time in range 3.9 – 10mmol/L.
Timepoint [7] 448674 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [8] 448675 0
Glycaemic control as measured by proportion of participants meeting the glycaemic target of having a glycated hemoglobin (HbA1c) result of less than 53mmol/mol.
Timepoint [8] 448675 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [9] 448676 0
Glycaemic control as measured by sensor glucose concentration.
Timepoint [9] 448676 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [10] 448677 0
Glucose levels during the day (0600-2359 hours).
Timepoint [10] 448677 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [11] 448678 0
Glucose levels during the night (0000 to 0559 hours).
Timepoint [11] 448678 0
At baseline, and at 6, 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [12] 448679 0
Glycaemic control as measured by glycated hemoglobin (HbA1c) from blood samples.
Timepoint [12] 448679 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [13] 448680 0
Safety of investigational system
Timepoint [13] 448680 0
Continuously from start of baseline to end of study at 39 weeks post-intervention commencement.
Secondary outcome [14] 448681 0
Safety of investigational system
Timepoint [14] 448681 0
Continuously from start of baseline to end of study at 39 weeks post-intervention commencement.
Secondary outcome [15] 448682 0
The change in diabetes impact.
Timepoint [15] 448682 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [16] 448683 0
The change in fear of hypoglycaemia
Timepoint [16] 448683 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [17] 448684 0
The change in diabetes treatment satisfaction
Timepoint [17] 448684 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [18] 448685 0
Platform performance as measured by percentage of time of sensor wear
Timepoint [18] 448685 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [19] 448686 0
Platform performance as measured by percentage of insulin delivery distribution.
Timepoint [19] 448686 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [20] 448687 0
Platform performance as measured by alarm frequency.
Timepoint [20] 448687 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [21] 448688 0
Platform performance as measured by amount of carbohydrates entered.
Timepoint [21] 448688 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [22] 448689 0
Assessment of lived participant experiences.
Timepoint [22] 448689 0
At 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [23] 448690 0
Changes in body composition
Timepoint [23] 448690 0
At 26 and 39 weeks post-RCT commencement.
Secondary outcome [24] 448693 0
Fibre intake
Timepoint [24] 448693 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [25] 448694 0
Energy intake
Timepoint [25] 448694 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.
Secondary outcome [26] 449778 0
The change in device satisfaction.
Timepoint [26] 449778 0
At baseline, and at 13 , 26, and 39 weeks post-RCT commencement.

Eligibility
Key inclusion criteria
1) Adult, any gender, aged 16-75 years, inclusive on day of consent.
2) Current HbA1c greater than or equal to 53 mmol/mol (7.0%) and lower than or equal to 86mmol/mol (10%)
3) Type 1 diabetes as per the American Diabetes Association Classification, diagnosed at least 12 months prior to Study Day 1.
4) Minimum daily insulin requirement of greater than or equal to 10 units/day
5) Willing and able to adhere to the study protocol.
6) Access to the internet and a computer or phone system that meets requirements for uploading the study pump.

Additional criteria for use of Tirzepatide in Phase 3:
1. Participation in Phases 1 and 2 of this three-phase study.
2. BMI greater than or equal to -1 standard deviation score
3. Participants not meeting the pre-defined glycaemic targets (TIR greater than or equal to 85% and TITR greater than or equal to 65%).
Minimum age
16 Years
Maximum age
75 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Not already using commercial Automated Insulin Delivery
2) Any severe diabetes related complications
3) Currently on a low carbohydrate diet (less than 50g carbohydrates/day).
4) Severe medical or psychiatric co-morbidity/severe mental illness
5) Participation in another device or drug study that could affect glucose measurements.
6) Plans to permanently leave study site regions prior to study completion.
7) If participant is of child-bearing potential, is pregnant or plans to become pregnant while participating in the study. A positive urine pregnancy test at Screening is exclusionary.
8) Any clinically significant pre-existing medical condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the investigator, pose an unacceptable risk to the subject in this study.

Additional criteria for use of Tirzepatide in Phase 3:
1. Significant gastrointestinal symptoms of pathology (inflammatory bowel disease), which in the opinion of investigators would pose an unacceptable risk to the participant.
2. Personal or family history of medullary thyroid carcinoma. Multiple endocrine neoplasia syndrome type 2.

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)
Allocation will be done by a biostatistician blinded to allocation arm and will use non-informative group codes until all planned analyses are completed. Once the REDCap (Research Data Capture) project is moved to production, the randomization list is locked and becomes unmodifiable and inaccessible to the study team preserving allocation concealment. The study statistician will have no contact with potential participants or be able to influence enrolment in any way.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Assignment during the 13-week RCT (Phase 1) is parallel (1:1 ratio; intervention group and control group), followed by a second randomization (1:1 ratio; stratified by Phase 1 randomization) during the Adaptive Phase 3.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Descriptive statistics will be calculated for all variables. The primary outcome will be the mean difference between groups in the change in TIR over 13 weeks. The mean difference, 95% confidence interval, and p-value will be estimated using a mixed effects regression model, adjusted for baseline TIR, and including a random effect for study site. Secondary outcomes include standard glycaemic metrics, HbA1c, system use, safety, and psychosocial variables assessed using Poisson and linear mixed models as appropriate. Residuals of all models will be plotted and visually assessed for homoskedasticity and normality. Statistical analysis will be performed using Stata software with two-sided p < 0.05 considered significant.
Exploratory analyses will be undertaken for the subsequent phases of the study, taking a descriptive (rather than inferential) approach, and will account for previous phases in the analyses, carrying out within-person analyses as appropriate.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
11/08/2025
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment outside Australia
Country [1] 27115 0
New Zealand
State/province [1] 27115 0

Funding & Sponsors
Funding source category [1] 319197 0
Government body
Name [1] 319197 0
Department of Internal Affairs - Lottery Grants Board
Country [1] 319197 0
New Zealand
Funding source category [2] 319199 0
University
Name [2] 319199 0
University of Otago
Country [2] 319199 0
New Zealand
Funding source category [3] 319200 0
Charities/Societies/Foundations
Name [3] 319200 0
Freemasons New Zealand
Country [3] 319200 0
New Zealand
Primary sponsor type
University
Name
University of Otago
Address
Country
New Zealand
Secondary sponsor category [1] 321665 0
None
Name [1] 321665 0
Address [1] 321665 0
Country [1] 321665 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317779 0
Northern B Health and Disability Ethics Committee 
Ethics committee address [1] 317779 0
Ethics committee country [1] 317779 0
New Zealand
Date submitted for ethics approval [1] 317779 0
12/06/2025
Approval date [1] 317779 0
Ethics approval number [1] 317779 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142122 0
Prof Benjamin J Wheeler
Address 142122 0
Department of Paediatrics and Child Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand
Country 142122 0
New Zealand
Phone 142122 0
+64 274701980
Fax 142122 0
Email 142122 0
[email protected]
Contact person for public queries
Name 142123 0
Benjamin J Wheeler
Address 142123 0
Department of Paediatrics and Child Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand
Country 142123 0
New Zealand
Phone 142123 0
+64 274701980
Fax 142123 0
Email 142123 0
[email protected]
Contact person for scientific queries
Name 142124 0
Benjamin J Wheeler
Address 142124 0
Department of Paediatrics and Child Health Otago Medical School - Dunedin Campus PO Box 56 Dunedin 9054 New Zealand
Country 142124 0
New Zealand
Phone 142124 0
+64 274701980
Fax 142124 0
Email 142124 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.