Medtronic Minimed Overnight Closed-Loop System
Condition: Type 1 Diabetes Mellitus; Autoimmune Diabetes; Juvenile-Onset Diabetes; Diabetes, Mellitus, Type 1
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional

Summary: 
      To test the function and safety of the Medtronic Overnight Closed Loop (OCL) System in a
      closely monitored 12 hour overnight inpatient study. Once the safety of the device has been
      validated we will move the study to an outpatient diabetes camp setting. The camp setting
      will allow us to obtain pilot efficacy and safety data in a "real-life" environment.

      We plan to compare the subject control nights to the subject nights on the OCL system to
      assess the percent of sensor glucose readings in the target range of 70-150 mg/dl. Based on
      previous research, we anticipate that the use of the OCL system will contribute to a greater
      percentage of sensor glucose readings in the target range.
    

Detailed description: 
      The steps are the same for the inpatient and camp studies, except that during the inpatient
      study subjects will have an IV inserted and blood samples will be obtained every 1/2 hour
      overnight. They will also have 20-30 minutes of activity in the afternoon and evening. After
      16 subjects have entered the inpatient study, their data will be sent to the DSMB (Data
      Safety Monitoring Board) for review. If the studies show that these studies have met our
      predefined safety criteria, and the DSMB approves, we will then conduct our outpatient
      studies.

      Step 1:

      Subjects who are eligible for the study (camp or inpatient hospital) will be contacted by
      phone and email, the study will be explained to them, and after written consent is obtained,
      they will be enrolled in the study. They will be mailed a Bayer Next meter, control
      solutions, and glucose test strips.

      Step 2: The will perform quality control test on the meter using the control solutions, and
      email these results to the study coordinator. For the week prior to the research center
      admission or camp they will be asked to use the Bayer meter to obtain two fasting glucose
      levels 20 minutes apart. They will be called by the study coordinator 3-5 days prior to
      admission to review these blood glucose testing requirements with the family. Subjects who
      have at least 3 days of data will be eligible for study participation.

      Step 3: On arrival to the hospital, camp or bus stop subjects will bring an original informed
      consent signed by both parents and/or guardians if less than 18 years old. This generally
      occurs between 10 AM and noon at the camps, and we will have them arrive before lunch to the
      research center.

      Step 4: The will have lunch, and within the first 3 hours after lunch (or within 3 hours of
      arrival to camp or the research center) they will have a history, limited physical exam and
      an A1c level and pregnancy test if female.

      They will be assigned a unique 5 digit identifier: The first digit is for the camp session;
      the next two digits are for their cabin number; and the last two digits are for their subject
      ID (identification). Subject 30804 would be in camp session 3, assigned to cabin 8, and
      subject 4. All subjects enrolled will be assigned a subject ID which progressively increases
      across all camp sessions, i.e. during the summer there will be only one subject #4.

      Step 5: Their Medtronic pump (from home) and Bayer meter will be uploaded. Two Enlite sensor
      will be used during the inpatient study. Only one Enlite sensor will be used during the camp
      phase of the study. All sensors will be inserted before 3pm and subjects will be given a
      study pump, and all their pump settings will be transferred to the study Revel 2.0 Medtronic
      Insulin Pump. They will receive training on the study pump and Enlite sensors. The CGM
      training will be done as a group session and will consist of the standard teaching which we
      developed for the JDRF (Juvenile Diabetes Research Foundation) randomized clinical trial.
      Insulin doses are only given by camp medical staff (including all correction doses), we will
      not use predictive alarms. Alarm thresholds will be set for 70 and 250 mg/dl during the day
      and on control nights. When the CLP is active at night, the local alarms on the Revel 2.0
      pump will be turned off. There will be no rate of change alarms. There active insulin time
      will be set to 6 hours. This will probably be different from their usual setting, and this
      will be explained to that this setting is for safety purposes during this study. The bolus
      wizard feature of the pump will be turned on and used for all insulin doses. They may use the
      type of meal boluses they would routinely use for meals at home (standard and/or dual wave or
      square wave boluses).

      Step 6: Data from their pump and meter download will be used to initialize the CLP. These
      initialization parameters will be entered into the Android phone assigned to them (which will
      remain with study staff). Their name will taped onto the phone, their study pump, home pump
      and meter using a labeler. The date and time will be entered into each device so they are all
      times are synchronized to the nearest minute.

      Step 7: At camp they will be randomized by cabins, so that an equal number of campers will be
      assigned to have active closed-loop control on the first night or be in the control arm on
      the first night. Thereafter campers in each arm will alternate between receiving closed and
      open loop intervention nights.

      Step 8: The Enlite sensor(s) will be calibrated 2 hours after insertion, before dinner and at
      9 PM if there are no rate of change arrows at these times on the first day. Thereafter
      calibration values will be entered before meals and before the 9 PM snack if there are no
      rate of change arrows. These finger sticks are done under supervision of a counselor who
      makes sure that their hands are either washed or the finger is cleaned with alcohol and
      allowed to dry before the finger prick.

      Step 9: At camp there will be evening activities after dinner, which can range from
      "capture-the-flag", scavenger hunts, dances, campfires, and other activities. During the
      inpatient hospital stay we will have some activity after dinner between 7-8 PM where subjects
      will wear a heart rate monitor with the goal of achieving an elevated heart rate which varies
      between 100 to 140 bpm for 20 - 30 minutes. This may be accomplished using an exercise
      treadmill or bicycle, or other aerobic activities (jumping jacks, stair climbing, brief
      sprints, etc.). The goal is to have some evening activities that mimic some of the variable
      activities that occur at camp, so that they are not sedentary after dinner.

      Step 11: On arrival to their cabins after evening activities those assigned to closed-loop
      control will have their CLP systems activated. In the hospital this will begin at 9 PM.

        1. The OCL system parameters on the Android controller are set to the values listed on the
           subject-specific OCL parameter document. These are verified by two study personnel
           cross-checking each other.

        2. A fingerstick glucose will be obtained and entered into the CLP. The meter glucose must
           be between 70 to 350 mg/dl for the OCL to be activated. At the same time a serum ketone
           test will be obtained with a Precision Xtra meter or a NovaStat meter and the serum
           ketones must be ≤ 0.6 mmol/L to proceed with the study.

        3. The Translator, Revel 2.0 Insulin Pump and MiniLink must be within 6 feet of each other.
           The OCL controller (on Android platform) will be in the subject/campers room/cabin but
           they will not have direct contact with the controller.

        4. The OCL will be activated. The system may not activate if the sensor and meter glucose
           readings show a greater than 20% difference. In this case the threshold alarms on the
           pump will be activated at 70 and 250 mg/dl and the OCL will not be used.

      Step 12: The CLP (Closed Loop Platform, Android phone) will establish communication with the
      intranet at camp and remote monitoring will be confirmed by viewing data on a iPAD connected
      to the camp intranet. In the hospital CLP will establish communication with the hospital
      intranet service, and remote monitoring will be confirmed on a computer outside the patients
      room and on an iPAD.

      Step 14: Patient management decisions based on meter glucose readings (and possible ketone
      readings during the study).
    

Intervention name(s): Hybrid Closed-loop System; Sensor-augmented pump
Intervention type(s): Device; Device
Intervention description(s): Medtronic Revel insulin pump, Enlite 3 sensor, Minimed transmitter, PID-IFB (proportional-integral-derivative based with insulin feedback) algorithm on an Android platform with remote monitoring.; Medtronic Revel insulin pump, Enlite 3 sensor, Minimed transmitter.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Diabetes; Insulin; Closed loop; Nocturnal glucose control