Project Nightlight: Efficacy and System Acceptance of Dinner/Night vs. 24hr Closed Loop Control

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), Roche Diagnostic Ltd., TypeZero Technologies, LLC, Tandem Diabetes Care, Inc., DexCom, Inc.

The purpose of this study is to use an investigational type of technology called Closed-Loop Control (CLC) Medical Platform System to help control blood sugar in people with type 1 diabetes mellitus in a home setting.

The CLC is an "artificial pancreas" (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive.These functionalities occur in a randomized cross-over design, each occurring for 8 weeks. These modalities are: SAP=sensor-augmented pump only USS+SAP (d)= Evening and Overnight Closed-Loop Control=SAP during day and CLC starting at dinner and continuing overnight USS+CLC (d)= 24/7 Closed-Loop Control=24-hour Day and Night Closed Loop Control

Closed-Loop Control (CLC), Sensor-Augmented Therapy (SAP), USS Virginia, Continuous Glucose Monitor (CGM), Insulin Pump, Artificial Pancreas (AP)

Order of intervention will be 1) SAP; 2) USS + SAP(d); 3) USS +CLC (d); 4) USS + SAP(d) SAP=sensor-augmented pump only USS+SAP (d)= Evening and Overnight Closed-Loop Control=SAP during day and CLC starting at dinner and continuing overnight USS+CLC (d)= 24/7 Closed-Loop Control=24-hour Day and Night Closed Loop Control

Order of intervention will be 1)USS + SAP(d) ; 2)USS +CLC (d); 3) USS + SAP(d); 4) SAP SAP=sensor-augmented pump only USS+SAP (d)= Evening and Overnight Closed-Loop Control=SAP during day and CLC starting at dinner and continuing overnight USS+CLC (d)= 24/7 Closed-Loop Control=24-hour Day and Night Closed Loop Control

The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive.

Overnight CLC achieved by USS+SAP(d) (also known at Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c < 7.5% vs ≥7.5% and time of day.

Overnight CLC achieved by USS+SAP(d) (also known as Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c < 7.5% vs ≥7.5% and time of day.

Index measure of low blood glucose risk. This is an index that indicates risk of hypoglycemia with low values indicating lower risk of hypoglycemia (particularly values 1 or lower).

Inclusion Criteria: type 1 diabetes for at least one year using insulin for at least 1 year an insulin pump for at least 6 months willingness to switch to lispro (Humalog) or aspart (Novolog) if using glulisine (Apidra). Exclusion Criteria: a medical condition or being been treated with medications that might interfere with the study

Kovatchev BP, Kollar L, Anderson SM, Barnett C, Breton MD, Carr K, Gildersleeve R, Oliveri MC, Wakeman CA, Brown SA. Evening and overnight closed-loop control versus 24/7 continuous closed-loop control for type 1 diabetes: a randomised crossover trial. Lancet Digit Health. 2020 Feb;2(2):e64-e73. doi: 10.1016/S2589-7500(19)30218-3. Epub 2020 Jan 3.