Prevention of Hypoglycemia After Exercise Using Closed Loop System in Children and Adolescents With Type 1 Diabetes
Prevention of Hypoglycemia After Exercise Using Closed Loop System in Children and Adolescents With Type 1 Diabetes
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.
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.
Inclusion Criteria:

 -  Informed consent signed by a parent/legal guardian and informed assent signed by the
 study participant prior study entry.

 -  Diagnosed with T1D, as defined by the American Diabetes Association and World Health
 Organization (ADA/WHO) for at least 1 year prior to study enrolment.

 -  Documented evidence should exist within the patient history of T1D.

 -  Age between 10 and 17 years (inclusive) at the time of enrolment.

 -  Treatment with insulin pump therapy for at least 3 months.

 -  HbA1C value ≤ 9% based on analysis from the local laboratory at the time of enrolment
 (A1C testing must follow National Glycohemoglobin Standardization Program (NGSP)
 standards).

 -  Willing to follow all study instructions (child and parent should be evaluated as one)

 -  Availability for the entire study duration and follow-up visits

 -  Willing to perform daily self-monitoring of blood glucose (SMBG) and required sensor
 calibrations

 -  If also present celiac/Hashimoto disease, the disease has to be adequately treated as
 determined by the investigator

 -  BMI above 5th centile and below 95th centile for age, respectively.

 Exclusion Criteria:

 -  Concomitant diseases that influence metabolic control (e.g. anemia, significantly
 impaired hepatic function, renal failure, history of adrenal insufficiency) or other
 medical conditions, which in the investigator's opinion, may compromise patient
 safety; Note: Adequately treated thyroid disease and celiac disease do not exclude
 subjects from enrollment.

 -  Significant co-morbidity that, in the opinion of the investigators would preclude
 participation in the study (e.g. current treatment for cancer, mental disorder)

 -  Any concomitant oral or parenteral glucocorticoids therapy within 1 month prior to
 screening, or planning to take oral or parenteral glucocorticoids during the study.
 (Exceptions: Short term oral glucocorticoids up to 7 days, inhaled steroids).

 -  Any concomitant therapy with antidiabetic agents or other medications, which could be
 a contraindication to participation in the study by the judgment of the investigator.

 -  Participation in another study of a medical device or drug that could affect glucose
 measurements or glucose management or Receipt of any investigational medical product
 within 1 month prior to screening (Visit 1).

 -  Female subject of child-bearing potential who is pregnant, breast-feeding, or planning
 to become pregnant during the study.

 -  Subject that has known hypoglycemic unawareness or recurrent severe hypoglycemic
 events with seizure and/or coma (more than two episodes) within 6 months prior to
 screening.

 -  History of one or more episodes of Diabetic Ketoacidosis (DKA) requiring
 hospitalization within a month prior to the screening.

 -  Current or recent history of alcohol or drug abuse.

 -  Visual impairment or hearing loss, which in the investigator's opinion, may compromise
 patient ability to perform study procedures safely (child and parent should be
 evaluated as a unit).