More Than 1 Year of Hybrid Closed Loop in Pediatrics. Gregory P. Forlenza, MD Assistant Professor Barbara Davis Center

Transcription

1 More Than 1 Year of Hybrid Closed Loop in Pediatrics Gregory P. Forlenza, MD Assistant Professor Barbara Davis Center

2 Disclosure Dr. Forlenza has served as a consultant for Abbott Diabetes Care and conducts research sponsored by Tandem Diabetes Care, Medtronic MiniMed, Dexcom, Insulet, TypeZero Technologies, Bigfoot Biomedical, and Animas. This presentation contains unpublished data being prepared for publication. Please do not take photos.

3 Objectives Identify the new features of the Medtronic 670G artificial pancreas and review how to modify various parameters. Analyze completed study results of the 670G system in pediatric populations and compare results in children against results in adults. Discussion, review, and clarification of presented information

4 Overview of 670G HCL Artificial Pancreas

5 Artificial Pancreas What is an artificial pancreas? 4. Insulin Dosing Algorithm(s) 3. CGM 1. Insulin Pump 5. ± Communication Device 2. Rapid Acting Insulin ± Glucagon

6 Medtronic 670G Artificial Pancreas The 670G is a Hybrid Closed Loop (HCL) system running a modified PID algorithm. Patients must bolus insulin for meals but the algorithm controls the basal rates in the background Commercially approved by the FDA on September 28 th, 2016 for use in patients 14+ years old with T1D. Studies down to 2 years old ongoing.

7 Medtronic 670G Artificial Pancreas Can set the following parameters In Open Loop Mode Basal Rates I:C ratio Correction Sensitivity Correction Target Active Insulin Time In Closed Loop Mode I:C ratio Active Insulin Time System Sets the following In Closed Loop Mode Basal rates modulate every 5 minutes based on epid Sensitivity is calculated as 1800/TDD Target is set as 120 and can be changed to 150 in exercise mode

8 Medtronic 670G Alerts and Safe Basal Safe Basal Pump administers a fixed basal rate (high rate or low rate depending on why it exited auto mode) Minimum delivery for 2.5 hours Time for these can be reset by Maximum delivery for 4 hours entering a BG value Sensor is reading lower than actual glucose Sensor error of 35% Senor is changed (2 hour warm up) Lost sensor signal for > 5 min Exiting Auto Mode The pump will exit Auto Mode of it has been in Safe Basal for 90 min High Alert: CGM > 300 mg/dl x 1 hour or > 250 mg/dl x 3 hours The high alerts exit auto mode automatically, pump never goes into safe basal Low Alert: CGM < 50 mg/dl

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10 Results of Pivotal Trial

11 670G Pivotal Trial Results Three month home-use trial of 670G in patients years old at 10 sites. Though not a controlled trial, authors compared data from the 2 week run-in period to data from the 3 month study period to show efficacy. Richard Bergenstal, Satish Garg, Stuart Weinzimer, Bruce Buckingham, Bruce Bode, William Tamborlane, Francine Kaufman

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14 1 year follow Up Data Remember: Participants enrolled in a 3 month intensive study period, after which they entered a long-term continuation phase. At BDC in peds we had 10 of 12 subjects enter the continuation phase Time Period HbA1c Change from Baseline Baseline 8.0 ± 0.8 n/a 1 month 7.9 ± month 7.0 ± 0.5 < month 7.3 ± 0.6 < month 7.5 ± month 8.1 ±

15 HbA1c Changes Over Time

16 Optimizing 670G in Clinical Practice

17 Optimizing HCL in Peds Together with our partners at Stanford and Yale, Laurel Messer and I are working on analyzing how 670G tuning parameters were modified during the pivotal trial and how this impacted CL control in pediatric patients. Table 1. Demographics Characteristic Value Subjects (n) 31 Age at Enrollment (yr) 17.8 ± 3.9 T1D Duration (yr) 9.3 ± 5.5 Enrollment HbA1c (%) 7.8 ± Month HbA1c (%) 7.1 ± 0.6 Gender (%) M 52 F 48 BMI (kg/m 2 ) 23.4 ± 3.6 Continuation Phase Participants (%) 87

18 Insulin Delivery and Time in Range, CL versus OL Mean TDD Mean basal/autobasal insulin Mean bolus insulin %basal/bolus split Mean 24-hour basal program Period Mean SD p-value change from baseline Baseline 58.6 ± 19.1 n/a Days ± Days ± Days ± Days ± Baseline 25.8 ± 8.3 n/a Days ± Days ± Days ± Days ± Baseline 32.6 ± 13.7 n/a Days ± Days ± Days ± Days ± Baseline 45.1 ± 9.2 n/a Days ± Days ± Days ± Days ± Baseline 26.7 ± 8.8 n/a Days ± Days ± Days ± Days ±

19 Insulin Delivery and Time in Range, CL versus OL Period Mean SD p-value change from baseline Baseline 7.9 ± 2.7 n/a Days ± am C:I ratio Days ± Days ± 2.7 < Days ± 2.8 < Baseline 8.9 ± 3.3 n/a Days ± pm C:I ratio Days ± 2.9 < Days ± 3.0 < Days ± 3.1 < Baseline 8.7 ± 3.4 n/a Days ± 3.1 < pm C:I ratio Days ± 2.7 < Days ± 2.7 < Days ± 2.6 < Baseline ± 51.6 n/a Days ± Insulin Action Time (min) Days ± Days ±

20 Insulin Delivery and Time in Range, CL versus OL % time in range mg/dl overall % time in range mg/dl auto mode % time in range mg/dl open loop Period Mean SD p-value change from baseline Baseline 55.3 ± 14.9 n/a Days ± 11.5 < Days ± 10.1 < Days ± 8.9 < Days ± 12.0 < Baseline n/a n/a Days ± 10.6 n/a Days ± 8.5 n/a Days ± 8.1 n/a Days ± 10.3 n/a Baseline 55.3 ± 14.9 n/a Days ± Days ± Days ± Days ±

21 Auto-mode/Manual Mode Times and Events during Study Mean SD Days ± 10.8 % time in auto mode Days ± 15.5 Days ± 14.2 Days ± 23.3 Days ± 2.7 Mean number of events removing pt from auto Days ± 2.5 mode per week (user-initiated and system) Days ± 1.9 Days ± 2.6 Mean number of events removing pt from auto mode per week (system) Mean number of events removing pt from auto mode per week (user initiated) % of events removing pt from auto mode related to safe basal time outs % of events removing pt from auto mode related to other alerts % of events removing pt from auto mode related to pt removing self Days ± 2.9 Days ± 2.6 Days ± 2.1 Days ± 2.8 Days ± 0.7 Days ± 0.6 Days ± 0.6 Days ± 0.5 Days ± 23.5 Days ± 21.3 Days ± 25.7 Days ± 28.5 Days ± 23.4 Days ± 18.5 Days ± 20.1 Days ± 25.0 Days ± 17.8 Days ± 13.1 Days ± 15.2 Days ± 20.3

22 Correlation of Time in Range with Time in Auto Mode

23 670G at an ADA Diabetes Camp in 2017

24 670G at Diabetes Camp The 670G uses a 6 day look back period to calculate TDD which is used to determine the behavior of the auto-basal and correction function when in Auto Mode. We generally cut insulin doses by 10-25% when patients arrive at camp due to increased physical activity. Additionally, Camp Colorado is at 9000 ft, and altitude generally decreases insulin requirements. We were concerned that the retrospective nature of the 607G would produce hypoglycemia and failure of AP at camp.

25 670G at Camp What did we do? Decreased I:C ratio by 35% (e.g. 1:8 to 1:10) at arrival. Increased IOB time by 1 hour (e.g. 2.5 to 3.4 hours) to help prevent over correction. Set temp target for first 24 hours and periodically reassessed based on activity for the day (changes target from 120 to 150 mg/dl). Changed conventional pump settings for backup as usual Decreased basal rates by 25% Decreased sensitivity by 25% Increased targets to 150 day and 200 mg/dl at night

26 670G at Camp It worked!!!! Hard to see but every pump has a blue shield! Will show data for 4 patients who have uploaded since camp

27 670G at Camp Data by Period 6 days Prior Camp 6 Days CGM Mean (mg/dl) ± ± 23.0 CGM StDev (mg/dl) 53.8 ± ± 17.2 CGM Cal/day 3.6 ± ± 1.5 CGM Use Per Day (%) 89.1 ± ± 12.0 Closed Loop Per Day (%) 81.8 ± ± 15.2 Hyperglycemia > 180 mg/dl (%) 30.1 ± ± 15.0 Target Range mg/dl (%) 67.9 ± ± 14.5 Hypoglycemia < 70 mg/dl (%) 2.0 ± ± 3.2 TDD (U/day) 50.6 ± ± 8.5 Basal/Auto-Basal (%) 45.8 ± ± 13.2 Bolus (%) 54.2 ± ± 13.2 Carbs per day (g) ± ± 85.1

28 Conclusions Data from the pivotal trial of 670G in pediatrics show significant benefits to time in range, hypoglycemia, and HbA1c. Changes to pump settings are necessary when starting to use the 670G. Improvements may wain overtime. Further work is needed to investigate these effects and how they may be mitigated.

29 Acknowledgements We would like to thank all of the participants who helped us conduct this trial. I would like to thank our excellent AP team at BDC: Robert Slover, R. Paul Wadwa, G. Todd Alonso, Laurel Messer, Cari Berget, Emily Jost, Samantha Lange, Lindsey Towers, Katie Thivener, Maninder Sethi, and Emily Westfall I would also like to thank our partners at Stanford and Yale. I would like to thank Medtronic.