Reduction of Nocturnal Hypoglycemia and Hyperglycemia in the Home Using Predictive Algorithms, Pump Suspension, and Insulin Dosing in Children and Young Adolescents
Condition: Type 1 Diabetes; Hypoglycemia; Hyperglycemia; Artificial Pancreas
MeSH terms: Hypoglycemia; Hyperglycemia
Study type: Interventional
Phase: Phase 2

Summary: 
      Objective: to gain experience in children and younger adolescents with in-home use of an
      algorithm that will dose insulin to minimize projected hyperglycemia overnight in addition to
      suspending the pump if hypoglycemia is projected overnight and to obtain feasibility, safety,
      and initial efficacy data

      Study Design: randomized controlled trial, with randomization on a night level within subject
      Patient Population: Youth 6.0 - <15 years old with type 1 diabetes treated with daily insulin
      therapy for at least one year and an insulin infusion pump for at least 6 months who have
      HbA1c < 10.0%.

      Sample Size: 30 subjects

      Study Duration and Visit Schedule: duration approximately 3 months, with preliminary run-in
      activities followed by up to 90 days spent in clinical trial phase of study; clinic visits at
      enrollment, following CGM and system assessment run-in phases, at start of clinical trial
      phase, at 21-day point of clinical trial phase, and after 42 nights of successful system use

      Major Efficacy Outcomes:

        -  Primary: time in range (70-180 mg/dl, 3.9-10.0 mmol/L) overnight.

        -  Secondary: time spent in hypoglycemia (<70 mg/dl, 3.9 mmol/L) and time spent in
           hyperglycemia (>180 mg/dl, 10.0 mmol/L) overnight.

      Major Safety Outcomes: CGM measures of hypo- and hyperglycemia, including morning blood
      glucose and mean overnight sensor glucose; adverse events including severe hypoglycemia and
      diabetic ketoacidosis
    

Detailed description: 
      Subjects who are eligible for the clinical trial initially will use a Veo insulin pump and
      Enlite CGM sensor at home for a minimum of 6 days/week over a 2-week period to verify that
      the subject is able to use the CGM and insert sensors.

      The first 10 subjects enrolled will be 11 to <15 years of age and will participate in an
      Algorithm Assessment Phase of approximately 10 nights of system use each with PLGS and Hyper
      Minimization active. Results of the approximate 100 nights will be reviewed with the study
      DSMB to assess safety and determine whether any adjustments to the algorithm parameters are
      needed. If adjustments are needed, the Algorithm Assessment Phase will be repeated with the
      same age restriction, using the same 10 subjects if possible. If no adjustments are needed
      and the DSMB judges it safe to continue the study, enrollment will continue across the full 6
      to <15 age range.

      Subjects who enroll in the study after the completion of the Algorithm Assessment Phase will
      use the closed-loop system at home for 5 nights of system use each with PLGS and Hyper
      Minimization active to demonstrate their ability to use the system and submit study data to
      the Coordinating Center.

      Subjects 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 in the home for approximately 42 nights:

        -  Each night the blood glucose 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 system will
           run in PLGS+Hyper Minimization mode or PLGS-only.

             -  Subjects will be blinded as to whether the system is running in PLGS+Hyper
                Minimization mode or PLGS-only.

             -  There will not be an alarm if the pump shuts off or if automated insulin dosing
                occurs. 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.

             -  The time period for outcome assessment each night will be from the time the system
                is activated until it is turned off in the morning.

             -  Pump shut off, when it occurs, will be for up to 120 minutes in a 150-minute
                period, and no more than 180 minutes for the entire night. Multiple instances of
                pump suspension can occur if there are recurrent predictions of hypoglycemia during
                the night.

        -  Small correction boluses of insulin will be delivered when the system predicts that
           hyperglycemia above a pre-set threshold will occur, with insulin-on-board constraints
           and cumulative delivery limits to minimize the likelihood of excessive insulin delivery.

        -  Subjects will be asked to check blood glucose with the study BG meter each morning prior
           to breakfast and enter the results using the controller software interface. The subject
           will be instructed to contact the study physician if the morning blood glucose value is
           <60 mg/dl (3.3 mmol/L) or >300 mg/dl (16.7 mmol/L). Monitoring processes will ensure
           that the subject can be contacted if these values are not reported as required or are
           out of range.

        -  Subjects will be asked to record all overnight carbohydrate intake using the controller
           software interface.

        -  Subjects will be asked to perform periodic CGM data uploads using the controller
           software interface. Monitoring processes will ensure that the subject can be contacted
           if these uploads do not occur as required, or if review of an upload reveals any
           extreme, prolonged episodes of hypoglycemia or hyperglycemia, or elevated morning blood
           glucose values.

      Once approximately 200 nights of randomized clinical trial phase data are available, the
      study DSMB will perform another data review to determine whether it is safe to continue the
      study. Subjects already using the study system at home will continue to use it during the
      DSMB review process, but no additional subjects will begin home use of the system until the
      DSMB review is complete.

      Upon completion of the study, subjects as well as study clinicians will be asked to complete
      a human factors usability questionnaire regarding use of the study system.

      There will be a follow-up (optional) extension phase for subjects who exhibit safe and
      competent use of the system at home. They may be given the option to continue home use of the
      system for up to 56 days to assess whether data-driven, subject-level customization of
      algorithm parameters improves glycemic outcomes compared with generic algorithm parameters
      that are identical for each subject.
    

Intervention name(s): Hyperglycemia Minimization Algorithm
Intervention type(s): Device
Intervention description(s): The hyperglycemia minimization algorithm will be running actively on the study laptop during the night and dose insulin if the algorithm predicts hyperglycemia. If hypoglycemia is predicted, the system will suspend the pump.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention