Prevention of Hypoglycemia After Exercise Using Closed Loop System in Children and Adolescents With Type 1 Diabetes
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional

Summary: 
      The Study will compare treatment with Closed Loop (CL) system - DreaMed MD-AID to the
      standard treatment without computer algorithm decisions - SAP therapy in 20 children and
      adolescents with Type 1 Diabetes (T1D) during and after afternoon physical activity.

      The aims of the study are:

        -  to demonstrate that the use of DreaMed MD-AID is safe during physical activity

        -  to investigate the risk of hypoglycemia among children and adolescents with T1D after
           afternoon exercise during closed-loop control.
    

Detailed description: 
      This is investigator initiated, single-center, open-label, crossover, randomized,
      interventional, in-hospital pediatric study, performed at the University Children's Hospital,
      University Medical Center Ljubljana.

      Study duration will be about 4 weeks per subject, 6 month overall. The study will compare
      Continuous Glucose Monitoring (CGM) based time in hypoglycemia in an intervention arm
      (Glucose control using DreaMed MD-AID) to a control arm (Glucose control using SAP).

      Each arm includes two exercise days with 1 week in-between. Subjects will be randomly
      assigned to participate first in the intervention arm (10 subjects) or first in the control
      arm (10 subjects). At the end of the first period patients will be asked to participate in
      another, i.e. the other arm with at least one week between arms.

      Subjects will be instructed to consume a similar diet and avoid caffeine, alcohol, and
      physical activity in the 48 hours before the exercise day visit.

      The start of the run-in period can be scheduled as a separate visit, but not more than 2 days
      after screening.

      All subjects will attend the clinic on six occasions:

        -  Visit 1: Screening and sensor/pump education, detailed physical examination will be
           performed, all subject will have to meet inclusion/exclusion criteria.

        -  Visit 2: Baseline assessment of the DreaMed MD-AID profile, subjects will perform
           resting electrocardiography (ECG) and determination of the maximal oxygen consumption
           rate (VO2max) on a cycle ergometer Ganshorn LF8.5G™ and Schiller software, with BG
           measurements before, at the end of the exercise and 2 hours after exercise. Subjects
           will be instructed to refrain from physical activity for 48 hours prior to visits 3 - 6.

        -  Visit 3: 24 hours DreaMed MD-AID or SAP with afternoon exercise (in the time between
           16:30 and 19:30): an i.v. catheter will be inserted in the antecubital or cephalic vein
           (for plasma BG and emergency). Cycle ergometer will be adjusted for each subject (work
           rate, seat height,..), they will be instructed to pedal at steady rate of 50-60
           rotations per minute (RPM).The subjects will cycle for 40 minutes at 55% Vo2max load
           (starting work rate set to 30 watts (W) with linear loading to reach 55% VO2max on 5:00
           minute exercise time) - the aim of this session is to induce delayed hypoglycemia.

        -  Visit 4: 24 hours DreaMed MD-AID or SAP with afternoon exercise (in the time between
           16:30 and 19:30): an i.v. catheter will be inserted in the antecubital or cephalic vein
           (for plasma BG and emergency). Cycle ergometer will be adjusted for each subject (work
           rate, seat height,..), they will be instructed to pedal at steady rate of 50-60
           rotations per minute (RPM). The subjects will cycle for 40minutes - high intensity
           interval training (2 - 6 sprints of 20 seconds at 80% VO2max with interval of 6 minutes
           low-moderate activity (55% VO2max (total of ~40 minutes) between the sprint. The aim of
           this session is to imitate children's physical activity (bursts of intensive physical
           activity interspersed with varying intervals of activity of low and moderate intensity.

        -  Visit 5&6: Same as visits 3 and 4, cross over from DreaMed MD-AID to SAP or vice versa.

      During the exercise, a continuous ECG will be recorded and inhaled O2 and exhaled Carbon
      Dioxide (CO2) will be measured.

      BG and lactate will be taken during the exercise visits: at the beginning of the exercise,
      after every 15 min exercise session, and every half an hour for the next 2 hours thereafter.

      All hypoglycemia will be confirmed with SBGM: glucose values <3.3 (60 mg/dl) mmol/l if
      symptomatic, and all hypoglycemia with self blood glucose monitoring (SBGM) values <2.8
      mmol/l (50 mg/dl) (regardless of symptoms) will be treated with rescue carbohydrates as per
      standard in-hospital procedure (15 g sugar per 10 kg of body weight (BW), re-evaluate and
      repeat if necessary in 15-30 minutes).

      New infusion set and two continuous glucose sensors (one for back-up) will be inserted in the
      subcutaneous tissue of the arm and then calibrated the day before each visit from 3 to 6.

      Schedule for all exercise days will be similar:

        -  12:00 hospital admission

        -  13:00 lunch

        -  13:30 to 16:00 rest

        -  16:00 afternoon snack

        -  16:30 to 19:30 exercise protocol

        -  19:45 dinner

        -  21:00 to 7:30 next day: bed time

        -  8:00 breakfast.

        -  13:00 lunch and end of study

      Subjects will have standardized and similar meals on all exercise days (lunch at 13:00,
      afternoon snack at 16:00, dinner at 19:45, and breakfast at 8:00 the next day), based on the
      weight, with calculated carbohydrates and calories: 1 gram of carbohydrates per kilogram, the
      content of the meal according to the recommendation: comprising of 50% carbohydrate, 20%
      protein, and 30% fat, of which no more than 10% will be saturated fat. During the exercise
      the SAP group will turn off the insulin pump and lower their basal insulin for 20% for the
      next 4 hours after the exercise.
    

Intervention name(s): DreaMed Substance Administration Device; Sensor Augmented Pump (SAP)
Intervention type(s): Device; Device
Intervention description(s): 2 exercise days under DreaMed MD-AID control with afternoon exercise (in the time between 16:30 and 19:30).
New infusion set and two continuous glucose sensors (one for back-up) will be inserted in the subcutaneous tissue of the arm and then calibrated the day before each visit from 3 to 6.
The continuous glucose sensor continuously will measure interstitial glucose levels and these values will be sent by the Minilink™ via wireless, low-powered, radio frequency to the Paradigm Veo every 5 minutes for up to 6 days.
The DreaMed MD-AID uses a vendor-supplied and self-developed (communication module) communication application programming interface (API) in order to retrieve glucose / insulin data from the Paradigm Veo and set insulin treatment according to the algorithm decision.; 2 exercise days under Sensor Augmented Pump with afternoon exercise (in the time between 16:30 and 19:30).
New infusion set and two continuous glucose sensors (one for back-up) will be inserted in the subcutaneous tissue of the arm and then calibrated the day before each visit from 3 to 6.
The continuous glucose sensor continuously will measure interstitial glucose levels and these values will be sent by the Minilink™ via wireless, low-powered, radio frequency to the Paradigm Veo every 5 minutes for up to 6 days.
During the exercise the group will turn off the insulin pump and lower their basal insulin for 20% for the next 4 hours after the exercise
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Investigator)
Primary purpose: Treatment