Type 1 Diabetes
Conditions
Keywords
Artificial pancreas, SAP therapy, children, adolescents, type 1 diabetes
Brief summary
The purpose of this study is to determine safety, feasibility and efficacy (with respect to sensor- augmented pump therapy) of an Artificial Pancreas (AP) prototype in day and night closed-loop control in children and adolescents with type 1 diabetes.
Detailed description
The AP prototype is based on a Modular Model Predictive Control algorithm (MMPC) implemented on the Diabetes Assistant (DiAs) wearable platform. The study will be divided in two parts: the first part will serve as a 3 days pilot study and will be conducted in a hotel/residence near the hospital. The investigators will recruit 6/8 children (5-12 years) and/or 6/8 adolescents (12-18 years), with type 1 diabetes who have experience with insulin pump. DiAs will be used 72 continuous hours of day and night. If part 1 will be successfully, after about 2-3 months, the study will move to the second part (the main part), that will consist in cross-over randomized study that will be conducted in a camp setting. The participants will be randomly assigned to the treatment arm (Artificial Pancreas) or to the control arm (sensor-augmented insulin pump). Then the same patient will be assigned to the other arm. Each treatment will be applied 3 consecutive days. During the first period (days 1-3) patients will do the same activites and will have the same diet as in the second period (day s 5-7). The investigators will recruit 30/40 children (5-12 years) and/or 30/40 adolescents (12-18 years), affected by type 1 diabetes who have experience with insulin pump therapy. The study has the permission of the Ethics Committee reference and the permission for clinical investigation with devices not CE marked by the Health Ministry.
Interventions
DEVICEartificial pancreas
Patients will be randomly assigned to receive either 3 days of automated closed-loop insulin delivery (intervention) followed by 3 days of sensor -augmented pump therapy (control), or the inverted sequence.
OTHERsensor augmented pump
During this control period (comparator arm) the patients will use sensor augmented pump. This period will be compared to the same period of artificial pancreas
Sponsors
University of Padova
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of type 1 diabetes · The diagnosis of type 1 diabetes is based on the investigator's judgment · C peptide levels and antibody determinations are not required 2. Daily insulin therapy for ≥ 12 months 3. Insulin pump therapy for ≥ 3 months 4. Age 6-18 years 5. A1C\<10 6. Avoidance of acetaminophen-containing medications (i.e. Tachipirina, tachidol, tachiflu) while wearing the continuous glucose monitor. 7. Willingness to wear a continuous glucose sensor 8. Female subjects who are sexually active must be on acceptable method of contraception (e.g. oral contraceptive pill, diaphragm, IUD).
Exclusion criteria
1. Diabetic ketoacidosis in the past month 2. Hypoglycemic seizure or loss of consciousness in the past 3 months 3. History of seizure disorder (except for hypoglycemic seizure) 4. A1C\>10 5. History of any heart disease including coronary artery disease, heart failure, or arrhythmias 6. Cystic fibrosis 7. Current use of oral glucocorticoids, beta-blockers or other medications, which in the judgment of the investigator would be a contraindication to participation in the study. 8. History of ongoing renal disease (other than microalbuminuria). 9. Subjects requiring intermediate or long-acting insulin (such as NPH, Detemir , Glargine or Degludec). 10. Subjects requiring other anti-diabetic medications other than insulin (oral or injectable). 11. Pregnancy - verbal denial of pregnancy obtained with telephone informed consent, pregnancy test performed at camp before study devices are assigned. 12. Sexually active females who do not practice acceptable contraceptive methods to prevent pregnancy. 13. Presence of a febrile illness within 24 hours of admission or acetaminophen use while wearing the CGM. The subject may be rescheduled for Research House/hotel admission if these criteria are not met. The camp study subject will not participate in the trial if these conditions are met. 14. 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 insufficiency * Alcohol abuse
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Spent With Blood Glucose < 3.9 mmol/L (or 70 mg/dl) | 3 days | percentage of time spent in hypoglicemia (\< 70 mg/dl or 3.9 mmol/L) both during day and night. All analyses will include a comparison of the results in Artificial Pancreas and SAP period |
| Percentage of Time Spent in Target Range (70-180 mg/dl or 3.9-10.0 mmol/L) | 3 days | percentage of time spent in target range (70-180 mg/dl or 3.9-10.0 mmol/L) both during day and night. All analyses will include a comparison of the results in Artificial pancraes and SAP period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Artificial Pancreas is Active | 3 days | percentage of time that the system worked without any technical problem |
Countries
Italy
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants Experimental arm: A closed-loop control system (artificial pancreas) will be used during night and day for 72 hours (3 days) with the aim of automate insulin infusion by an insulin pump to control glucose level. AP is composed of a CGM device (Dexcom G4), an insulin pump (Accu Chek Spirit combo, Roche), and a model predictive control algorithm that is embedded in a smartphone and wirelessly linked to the CGM device and insulin pump. A remote monitoring will be ensured all the time the AP will be active and study team will be present in the camp.
artificial pancreas: Patients will be randomly assigned to receive either 3 days of automated closed-loop insulin delivery (intervention) followed by 3 days of sensor -augmented pump therapy (control), or the inverted sequence. | 32 |
| Total | 32 |
Baseline characteristics
| Characteristic | All Study Participants |
|---|---|
| Age, Continuous | 7.6 years STANDARD_DEVIATION 1.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 32 Participants |
| Region of Enrollment Italy | 32 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
Percentage of Time Spent in Target Range (70-180 mg/dl or 3.9-10.0 mmol/L)
percentage of time spent in target range (70-180 mg/dl or 3.9-10.0 mmol/L) both during day and night. All analyses will include a comparison of the results in Artificial pancraes and SAP period
Time frame: 3 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CLOSED LOOP | Percentage of Time Spent in Target Range (70-180 mg/dl or 3.9-10.0 mmol/L) | 56.8 percentage | Standard Deviation 13.5 |
| OPEN LOOP | Percentage of Time Spent in Target Range (70-180 mg/dl or 3.9-10.0 mmol/L) | 63.1 percentage | Standard Deviation 11 |
Primary
Percentage of Time Spent With Blood Glucose < 3.9 mmol/L (or 70 mg/dl)
percentage of time spent in hypoglicemia (\< 70 mg/dl or 3.9 mmol/L) both during day and night. All analyses will include a comparison of the results in Artificial Pancreas and SAP period
Time frame: 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CLOSED LOOP | Percentage of Time Spent With Blood Glucose < 3.9 mmol/L (or 70 mg/dl) | 2 percentage |
| OPEN LOOP | Percentage of Time Spent With Blood Glucose < 3.9 mmol/L (or 70 mg/dl) | 6.7 percentage |
Secondary
Percentage of Time Artificial Pancreas is Active
percentage of time that the system worked without any technical problem
Time frame: 3 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CLOSED LOOP | Percentage of Time Artificial Pancreas is Active | 97 percentage of time |