Outpatient Reduction of Nocturnal Hypoglycemia by Using Predictive Algorithms and Pump Suspension in Children

Patients who are eligible for the clinical trial initially will use a Veo insulin pump and Enlite sensor at home to verify that the patient is able to use the continuous glucose monitor (CGM) and insert sensors and is eligible to continue in the study. A parent or guardian of the child subject will oversee the actions of the subject and be responsible for the patient's overall participation during the proposed study, including operation of the investigational device system.

The first 10 patients 8 to <15 years of age will participate in an Algorithm Assessment Phase of approximately 10 nights of active system use each (for a nominal total of 100 nights of use) to determine if any adjustments to the algorithm parameters are needed and if it is safe to advance to a randomized clinical trial phase with these subjects. If adjustments are needed, the Algorithm Assessment Phase will be repeated, using the same 10 patients if possible. Once the randomized clinical trial phase begins for patients 8 to <15 years of age, approximately 200 nights of randomized system use will be collected and assessed for safety before any patients 3 to <8 years of age may be enrolled in the study. When enrollment does begin for patients 3 to <8 years of age, a second Algorithm Assessment Phase will be conducted with the first 10 patients in that younger age group using the same approach described above for the older subjects. Once the randomized clinical trial phase begins for patients 3 to <8 years of age, a final Data Safety Monitoring Board safety assessment will be performed after approximately the first 200 nights of randomized system use.

Patients who enroll in the study after the completion of the Algorithm Assessment Phase for their age group will use the closed-loop system at home for at least 5 days to demonstrate their ability to use the system and submit study data to the Coordinating Center.

Patients who successfully demonstrate their ability to use the system at home as described above will be eligible for the randomized trial phase. This phase consists of use of the full system as an outpatient for approximately 42 nights:

• Each night the blood glucose (BG) level will be checked with the BG meter and used to perform a calibration of the CGM. This calibration must occur no more than 90 minutes prior to activation of the system. NOTE: Subjects will be instructed to calibrate the CGM per manufacturer guidelines.
• Then the system will be activated, linking the CGM and insulin pump to the computer at the bedside.
• A randomization schedule on the laptop will be used to determine whether the 'pump shut off' application will be active that night or not.
• Patients will be blinded as to whether the pump shut off is active when a session is initiated each night.
• There will not be an alarm if the pump shuts off. The CGM alarm will be set to 60 mg/dL (3.3 mmol/L). When a CGM alarm occurs, the subject will be asked to measure the blood glucose with a BG meter, if he/she is aware of the alarm.
• Patients will be asked to check blood ketones with the study ketone meter if the subject has a fingerstick BG ≥250 mg/dL (13.9 mmol/L).
• Patients will be asked to check blood glucose with the study BG meter, blood ketones with the study ketone meter, and urine ketones with a ketone strip each morning prior to breakfast and enter the results using the controller software interface. The patient will be instructed to contact the study physician if the blood glucose or ketone readings are out of an expected range.
• Patients will be asked to record all overnight carbohydrate intake using the controller software interface.
• Patients will be asked to perform periodic CGM data uploads using the controller software interface.

Upon completion of the study, patients as well as study clinicians will be asked to complete a human factors usability questionnaire regarding use of the study system.

Inclusion criteria

• Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year and an insulin infusion pump for at least 6 months
• Age 3 to <15 years
• HbA1c <=8.5%
• Availability of internet access for periodic upload of study data

Exclusion criteria

• Diabetic ketoacidosis in the past 3 months
• Hypoglycemic seizure or loss of consciousness in past 6 months
• History of seizure disorder (except for hypoglycemic seizures)
• Cystic fibrosis
• Current use of oral/inhaled glucocorticoids, beta-blockers or other medications, which in the judgment of the investigator would be a contraindication to participation in the study
• History of ongoing renal disease (other than microalbuminuria), or liver disease (Creatinine is > 1.5 mg/dL (132 µmol/L))
• Medical or psychiatric condition that in the judgment of the investigator might interfere with the completion of the protocol such as:

• Inpatient psychiatric treatment in the past 6 months
• Uncontrolled adrenal disorder
• Abuse of alcohol
• Pregnancy
• Liver disease as defined by an Alanine Aminotransferase Test (ALT) greater than 3 times the upper limit of normal