The FLIP-IT trial - Fully automated artificial pancreas in adults with previously above-target type 1 diabetes

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.

This is an, open-label three-phase study. Expected duration of total participant study participation is up to 54 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. Intervention group participants will subsequently commence Phase 2 described below. Control group participants will subsequently cross over to a delayed start of Patch-APS use, following identical training and remote settings review procedures as described below for the intervention arm. After 13 weeks, control participants will commence Phase 2. 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 13-week extension with participants not meeting pre-defined glycaemic targets (time in range [TIR] greater than 85% and time in tight range [TITR] greater than 60%) commencing use of Tirzepatide. 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 13 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 2-3 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, the intervention arm will commence a 13-week extension phase using Patch-APS 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). For control participants, this phase will start after completion of the 13-week Delayed Start Patch-APS phase. 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 commence 13 weeks of Tirzepatide. Participants meeting the glycaemic targets will continue use of the treatment from Phase 2 for further 13 weeks. 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.