Type1 Diabetes
Conditions
Keywords
type 1 diabetes, artificial pancreas, closed-loop, automated insulin delivery
Brief summary
The aim of this clinical study is to determine the feasibility, safety, and preliminary effectiveness of the Zone-Model Predictive Control Artificial Pancreas (ZMPC\_AP) system in pediatric subjects with type 1 diabetes in an ambulatory semi-supervised environment over a short duration of 3 days and 2 nights, or up to 60 hours.
Detailed description
The artificial pancreas platform employed under study is centered about the following four key innovations: 1) A zone model predictive control strategy that is at the same time very safe with respect to hypoglycemia, and can simultaneously and independently be tuned with respect to its response to hyperglycemia; 2) Zone control with diurnal blood-glucose target zones; 3) Models of insulin-glucose physiology and insulin on board; 4) A system for alarming and notification of impending hypoglycemia and technical malfunctions: the Health Monitoring System. These features have been evaluated in several clinical trials in adults with unannounced meals and exercise. The proposed study will evaluate enhancements to our previous system tailored for the special needs of pediatric subjects: 1) A control strategy with responses to hyperglycemia and hypoglycemia spanning wide ranges, as is typical with children; 2) The use of time-dependent zones specific for pediatric subjects; 3) The development of models for young children, capturing the greater physiologic variability, and ensuring cautious insulin delivery; 4) remote alarming and notification systems that are useful to parents.
Interventions
DEVICEZone-Model Predictive Control Artificial Pancreas (ZMPC_AP)
Zone-Model Predictive Control Artificial Pancreas (ZMPC\_AP)
Sponsors
Harvard University
Yale University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
SIngle arm cohort study
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Age 2- \<18 years; for first cohort(s), subjects will be 12-17 years; additional age brackets will be 8-11 years and then \<8 years 2. Type 1 diabetes for ≥ 1 year duration - the diagnosis of type 1 diabetes will be based on the history of ketosis/ketoacidosis at diagnosis or laboratory evidence of islet-cell auto-immunity 3. A1c level ≤ 10.0% 4. Use of insulin pump and carbohydrate counting for ≥ 3 months 5. Average total daily insulin dose of at least 10 units/day 6. Current or past use of Continuous Glucose Monitoring (CGM) is desirable but NOT required 7. Normal renal function as measured within 6 months of enrollment 8. Normal thyroid function within 6 months of enrollment, or if previously diagnosed with hypothyroidism, documented within 3 months of enrollment 9. Parent/guardian agrees to stay at hotel with subject for duration of hotel phase and has cell phone that can send/receive text messages 10. Subject and participating parent/guardian speak and comprehend English
Exclusion criteria
1. Episode of diabetic ketoacidosis (DKA) within 6 months of enrollment 2. Episode of severe hypoglycemia (seizure, loss of consciousness) within 6 months of enrollment 3. Use of medications (other than insulin) known to affect BG levels within 4 weeks of enrollment - examples include systemic glucocorticoids, metformin, pramlintide, liraglutide) 4. Current use of other medications, that in opinion of investigator, would interfere with safety or effectiveness of the study including acetaminophen 5. Medical disorder, that in opinion of investigator, would be contraindication for inclusion; hypothyroidism and celiac disease are NOT exclusion if under good control 6. Female subjects of childbearing potential unwilling to have pregnancy testing 7. Female subject currently pregnant or lactating 8. History of alcohol or drug abuse, documented eating disorder, or inpatient psychiatric treatment within 6 months of enrollment 9. Subject is currently participating in another research study involving an investigational drug or device
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL)) | 60 hours | Number of participants with more than one confirmed BG \< 50 mg/dL |
| Hyperglycemia Safety: Number of Participants With More Than Two Blood Glucose (BG) Readings > 300 mg/dL Longer Than 2 Hour or Any BG 400 > Milligrams/Deciliter (mg/dL)) | 60 hours | No more than two confirmed BG ≥ 300 mg/dL longer than 2 hours, and no BG ≥ 400 mg/dL, unless determined to be from an infusion site failure. |
| Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l | 60 hours | Number of participants with blood ketone level \> 1.0 mmol/l for longer than 2 hours, and no blood ketone level \>3.0 mmol/L, unless determined to be from an infusion site. failure |
| Safety: Number of Participants Who Experienced an Adverse Event | 60 hours | Adverse events include seizure, loss of consciousness, severe hypoglycemia, diabetic ketoacidosis |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Sensor Glucose Time in Hypoglycemia (<60 mg/dL) | 60 hours | Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 60 mg/dL |
| Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL) | 60 hours | Mean meter and sensor glucose levels (mg/dL) |
| Percent Time AP System Active | 60 hours | Percentage of time, over the whole evaluation period, during which the sensor and pump are determined to be wirelessly connected and communicating with each other, based on duration of alert and error messages indicated by the system |
| Percent Sensor Glucose Time in Hyperglycemia (>250 mg/dL) | 60 hours | Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 250 mg/dL |
| Percent Sensor Glucose Time in Range (70-180 mg/dL) | 60 hours | Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is between 70-180 mg/dL |
| Percent Sensor Glucose Time Below Range (<70 mg/dL) | 60 hours | Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 70 mg/dL |
| Percent Sensor Glucose Time Above Range (>180 mg/dL) | 60 hours | Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 180 mg/dL |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) Use Zone-Model Predictive Control Artificial Pancreas (ZMPC\_AP) system
Zone-Model Predictive Control Artificial Pancreas (ZMPC\_AP): Zone-Model Predictive Control Artificial Pancreas (ZMPC\_AP) | 20 |
| Total | 20 |
Baseline characteristics
| Characteristic | Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) |
|---|---|
| Age, Continuous | 11.3 years STANDARD_DEVIATION 3.6 |
| Baseline A1c | 7.6 percentage of HbA1c STANDARD_DEVIATION 0.9 |
| Duration of Type I Diabetes | 5.0 years STANDARD_DEVIATION 3.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 2 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 | 17 Participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 0 / 20 |
| serious Total, serious adverse events | 0 / 20 |
Outcome results
Primary
Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l
Number of participants with blood ketone level \> 1.0 mmol/l for longer than 2 hours, and no blood ketone level \>3.0 mmol/L, unless determined to be from an infusion site. failure
Time frame: 60 hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l | blood ketone levels > 1.0 mmol/l for longer than 2 hours | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l | blood ketone levels > 3.0 mmol/l | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Blood Ketone Safety: Number of Participants With Blood Ketone Levels > 1.0 mmol/l for Longer Than 2 Hours or Any Ketone Level> 3.0 mmol/l | blood ketone levels < 1.0 mmol/l for longer than 2 hours or blood ketone levels < 3.0 mmol/l | 20 Participants |
Primary
Hyperglycemia Safety: Number of Participants With More Than Two Blood Glucose (BG) Readings > 300 mg/dL Longer Than 2 Hour or Any BG 400 > Milligrams/Deciliter (mg/dL))
No more than two confirmed BG ≥ 300 mg/dL longer than 2 hours, and no BG ≥ 400 mg/dL, unless determined to be from an infusion site failure.
Time frame: 60 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Hyperglycemia Safety: Number of Participants With More Than Two Blood Glucose (BG) Readings > 300 mg/dL Longer Than 2 Hour or Any BG 400 > Milligrams/Deciliter (mg/dL)) | No more than 2 confirmed BG≥300 mg/dL > 2 hours and no BG≥400 mg/dL not due to infusion site failure | 19 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Hyperglycemia Safety: Number of Participants With More Than Two Blood Glucose (BG) Readings > 300 mg/dL Longer Than 2 Hour or Any BG 400 > Milligrams/Deciliter (mg/dL)) | More than 2 two confirmed BG ≥ 300 mg/dL >2 hours or BG ≥ 400 mg/dL not due to infusion site failure | 1 Participants |
Primary
Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL))
Number of participants with more than one confirmed BG \< 50 mg/dL
Time frame: 60 hours
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL)) | No more than one confirmed BG < 50 mg/dL | 19 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Hypoglycemia Safety: Number of Participants With Blood Glucose (BG)) Readings < 50 Milligrams/Deciliter (mg/dL)) | More than one confirmed BG < 50 mg/dL | 1 Participants |
Primary
Safety: Number of Participants Who Experienced an Adverse Event
Adverse events include seizure, loss of consciousness, severe hypoglycemia, diabetic ketoacidosis
Time frame: 60 hours
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Safety: Number of Participants Who Experienced an Adverse Event | seizures | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Safety: Number of Participants Who Experienced an Adverse Event | loss of consciousness | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Safety: Number of Participants Who Experienced an Adverse Event | severe hypoglycemia | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Safety: Number of Participants Who Experienced an Adverse Event | diabetic ketoacidosis | 0 Participants |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Safety: Number of Participants Who Experienced an Adverse Event | no adverse event | 20 Participants |
Secondary
Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL)
Mean meter and sensor glucose levels (mg/dL)
Time frame: 60 hours
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL) | Meter blood glucose | 161.4 mg/dL | Standard Deviation 39.8 |
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Mean Meter and Sensor Glucose Levels Milligram/Deciliter (mg/dL) | Sensor glucose | 172 mg/dL | Standard Deviation 26 |
Secondary
Percent Sensor Glucose Time Above Range (>180 mg/dL)
Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 180 mg/dL
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Sensor Glucose Time Above Range (>180 mg/dL) | 37.4 percentage of time | Standard Deviation 14.8 |
Secondary
Percent Sensor Glucose Time Below Range (<70 mg/dL)
Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 70 mg/dL
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Sensor Glucose Time Below Range (<70 mg/dL) | 1.8 percentage of time | Standard Deviation 1.4 |
Secondary
Percent Sensor Glucose Time in Hyperglycemia (>250 mg/dL)
Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is greater than 250 mg/dL
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Sensor Glucose Time in Hyperglycemia (>250 mg/dL) | 12.1 percentage of time | Standard Deviation 10.3 |
Secondary
Percent Sensor Glucose Time in Hypoglycemia (<60 mg/dL)
Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is below 60 mg/dL
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Sensor Glucose Time in Hypoglycemia (<60 mg/dL) | 0.6 percentage of time | Standard Deviation 0.7 |
Secondary
Percent Sensor Glucose Time in Range (70-180 mg/dL)
Percentage of time, over the whole evaluation period, during which the glucose level, as determined by the continuous glucose sensor, is between 70-180 mg/dL
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Sensor Glucose Time in Range (70-180 mg/dL) | 63.5 percentage of time | Standard Deviation 14.4 |
Secondary
Percent Time AP System Active
Percentage of time, over the whole evaluation period, during which the sensor and pump are determined to be wirelessly connected and communicating with each other, based on duration of alert and error messages indicated by the system
Time frame: 60 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Zone-Model Predictive Control Artificial Pancreas (ZMPC_AP) | Percent Time AP System Active | 92.7 percentage of time | Standard Deviation 7 |