Application of Zone Model Predictive Control Artificial Pancreas During Extended Use of Infusion Set and Sensor: A Randomized Crossover-Controlled Home-Use Trial

Abstract

Objective: As artificial pancreas (AP) becomes standard of care, consideration of extended use of insulin infusion sets (IIS) and continuous glucose monitors (CGMs) becomes vital. We conducted an outpatient randomized crossover study to test the safety and efficacy of a zone model predictive control (zone-MPC)-based AP system versus sensor augmented pump (SAP) therapy in which IIS and CGM failures were provoked via extended wear to 7 and 21 days, respectively.

Research design and methods: A smartphone-based AP system was used by 19 adults (median age 23 years [IQR 10], mean 8.0 ± 1.7% HbA_1c) over 2 weeks and compared with SAP therapy for 2 weeks in a crossover, unblinded outpatient study with remote monitoring in both study arms.

Results: AP improved percent time 70-140 mg/dL (48.1 vs. 39.2%; P = 0.016) and time 70-180 mg/dL (71.6 vs. 65.2%; P = 0.008) and decreased median glucose (141 vs. 153 mg/dL; P = 0.036) and glycemic variability (SD 52 vs. 55 mg/dL; P = 0.044) while decreasing percent time <70 mg/dL (1.3 vs. 2.7%; P = 0.001). AP also improved overnight control, as measured by mean glucose at 0600 h (140 vs. 158 mg/dL; P = 0.02). IIS failures (1.26 ± 1.44 vs. 0.78 ± 0.78 events; P = 0.13) and sensor failures (0.84 ± 0.6 vs. 1.1 ± 0.73 events; P = 0.25) were similar between AP and SAP arms. Higher percent time in closed loop was associated with better glycemic outcomes.

Conclusions: Zone-MPC significantly and safely improved glycemic control in a home-use environment despite prolonged CGM and IIS wear. This project represents the first home-use AP study attempting to provoke and detect component failure while successfully maintaining safety and effective glucose control.

Trial registration: ClinicalTrials.gov NCT02773875.

Figure 1

Paired comparison of mean glucose and time in target range (70–180 mg/dL) during SAP (control) and zone-MPC AP (experimental) arms. The solid lines connect individual subjects in this crossover study and display increase or decrease in the glycemic metric. The hypoglycemia exposure (time <70 mg/dL) is shown using a bubble with increased size signifying increased time in hypoglycemia during that arm. The dashed red line displays overall group results along with group mean as an annotation. The AP arm resulted in reduced mean BG (A) and improvement in time in range (B) for a majority of subjects (14 of 19). It also resulted in a decrease in time in hypoglycemia, as measured by time <70 mg/dL for the majority of subjects (18 of 19). Subjects are color coded with the same color between panels.

Figure 2

Plot of day-by-day mean glucose during SAP and zone-MPC AP arms. First and last day were excluded to include only days with a full 24 h of CGM data. The mean time <70 mg/dL is shown as varying size bubbles. The day-by-day mean glucose was lower during closed-loop use on 11 of 13 days.

Figure 3

Analysis on relationship between glycemic changes, from zone-MPC AP to SAP, and the percent time the closed loop was active. The outcomes considered are change in mean glucose (R² = 0.38, β₁ = −1.92 [P = 0.006], 95% CI −3.23, −0.60) (A) and change in percent time in 70–180 mg/dL range (R² = 0.32, β₁ = 1.49 [P = 0.012], 95% CI 0.35, 2.62) (B). The time spent in closed loop correlates with improvement in glycemic outcomes.