Diabetes Mellitus, Type 1
Conditions
Keywords
Artificial Pancreas Project, Diabetes Mellitus, Type 1, Insulin pump therapy, Continuous Glucose Monitors (CGM), Juvenile-Onset Diabetes, Autoimmune Diabetes, Closed-to-Range, Diabetes Assistant (DiAs)
Brief summary
The primary goal is to test the function of the Diabetes Assistant (DiAs) enhanced control-to-range (CTR) controller in a closely monitored diabetes camp setting. The camp setting will allow us to obtain pilot efficacy data.
Detailed description
The first phase of this study will test the feasibility of initializing the DiAs CTR system in a clinical research center. We will test the procedures that will occur with the camp studies, from consenting the subjects, obtaining morning glucose readings, initializing the sensor in the early afternoon, having some light activity in the evening, a bedtime snack, and initializing the closed-loop system within 30 minutes before they go to bed. We will also test how the system performs using the same calibration and blood glucose monitoring that will be done at camp. In the inpatient study we will mimic some camp activities by having the subjects have 20-30 minutes of aerobic activity in the afternoon and in the evening after dinner. The data from the inpatient studies will be reviewed by the Data Safety Monitoring Board (DSMB) before we proceed with the Phase 2 summer camp studies. The second phase of this proposal is the in-camp studies. The same health care providers that conducted the inpatient studies will be conducting the camp studies. They will be monitoring all campers on closed-loop control in real-time. Participants will be randomized to either closed-loop (experimental) or sensor-augmented therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session (i.e. on DiAs CTR every other night). Those assigned to DiAs CTR control will be remotely monitored throughout the night. Those assigned to the control group will not have remote monitoring overnight, but they will be wearing a Dexcom G4Platinum sensor with active low and high sensor glucose alarms. Initial studies will be done at a camp with older children and camp staff who are aged 15-35 years of age, with at least 5 subjects between 15 to 18 years old. If these studies are safe (after DSMB review) we will do additional camps and include children 10-14 years old.
Interventions
The Control-to-Range (CTR) algorithm that will be used in DiAs will automatically adjusts insulin delivery in response to CGM values that have exceeded or are predicted to exceed the bounds of a pre-specified blood glucose range.
DEVICETandem t:slim Insulin Pump
FDA, market-approved insulin pump.
FDA, market-approved continuous glucose monitor (CGM)
Sponsors
Stanford University
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
10 Years to 35 Years
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of type 1 diabetes and using daily insulin therapy for at least one year and a Medtronic, Animas or Tandem insulin infusion pump for at least 3 months 2. The diagnosis of type 1 diabetes is based on the investigator's judgment; C peptide levels and antibody determinations are not required. 3. Age 10.0 - 35 years 4. Willingness to use a Sure-T or Contact Detach infusion set while at camp
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. Using an OmniPod insulin infusion pump 5. History of any heart disease including coronary artery disease, heart failure, or arrhythmias 6. Cystic fibrosis 7. Current use of oral/inhaled 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. Insulin pump users who supplement with injected intermediate or long acting insulin. 10. Subjects who take other anti-diabetic medications other than insulin.. 11. Medical or psychiatric condition that in the judgment of the investigator might interfere with the completion of the protocol such as: 12. Inpatient psychiatric treatment in the past 6 months 13. Uncontrolled adrenal disorder 14. Abuse of alcohol 15. Pregnancy (verbal denial of pregnancy obtained with telephone informed consent, pregnancy test performed at camp before study devices are assigned). 16. Sexually active females who do not practice acceptable contraceptive methods to prevent pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Time Near Normoglycemia | 6 nights | Percent of time in a glucose target range of 70-150 mg/dl during camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overnight Glucose | 6 nights | Mean overnight glucose during camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group. |
| Glycemic Events | 6 nights | Number of nights with \>= 1 hypo- and hyperglycemic event occurring overnight during the camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inpatient Study The first phase of this study tested the feasibility of initializing the DiAs CTR system in a clinical research center. We tested the procedures that would occur with the camp studies, from consenting the subjects, obtaining morning glucose readings, initializing the sensor in the early afternoon, having some light activity in the evening, a bedtime snack, and initializing the closed-loop system within 30 minutes before they go to bed. We also tested how the system would perform using the same calibration and blood glucose monitoring that would be done at camp. In the inpatient study mimicked some camp activities by having the subjects have 20-30 minutes of aerobic activity in the afternoon and in the evening after dinner. The data from the inpatient studies was reviewed by the Data Safety Monitoring Board (DSMB) before we proceeded with the Phase 2 summer camp studies. | 12 |
| Camp Study The second phase of this proposal was the in-camp studies. The same health care providers that conducted the inpatient studies conducted the camp studies. They monitored all campers on closed-loop control in real-time. Participants were randomized to either closed-loop (experimental) or sensor-augmented therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session (i.e. on DiAs CTR every other night). Since participants were not always successfully completing a closed-loop control night, the pattern could not hold throughout the entire trial. Thus, there are numerous intervention sequences.
Those assigned to DiAs closed-loop control were remotely monitored throughout the night. Those assigned to the control group were not monitored remotely overnight, but they were wearing Dexcom G4 Platinum sensors with active low and high sensor glucose alarms. | 20 |
| Total | 32 |
Baseline characteristics
| Characteristic | Inpatient Study | Total | Camp Study |
|---|---|---|---|
| Age, Continuous | 15.3 years STANDARD_DEVIATION 2.1 | 15.3 years STANDARD_DEVIATION 2.6 | 15.3 years STANDARD_DEVIATION 2.9 |
| Diabetes Duration | 7.6 years STANDARD_DEVIATION 4.6 | 6.4 years STANDARD_DEVIATION 3.9 | 5.6 years STANDARD_DEVIATION 3.5 |
| HbA1c | 8.7 percent of glycated hemoglobin STANDARD_DEVIATION 0.7 | 8.4 percent of glycated hemoglobin STANDARD_DEVIATION 1 | 8.1 percent of glycated hemoglobin STANDARD_DEVIATION 1.1 |
| Sex: Female, Male Female | 6 Participants | 16 Participants | 10 Participants |
| Sex: Female, Male Male | 6 Participants | 16 Participants | 10 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 / 20 |
| serious Total, serious adverse events | 0 / 32 | 0 / 20 |
Outcome results
Primary
Percent Time Near Normoglycemia
Percent of time in a glucose target range of 70-150 mg/dl during camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group.
Time frame: 6 nights
Population: Data from OCL nights during which there were technical problems (infusion set failure, sensor error \>20%, pump failure with \>60-min interruption to closed-loop) were removed. Only nights with a minimum of 5h of OCL were included. For control, only data from nights where sensor error was \<20% with a minimum of 5h were included.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Experimental: Closed-Loop Control | Percent Time Near Normoglycemia | 73 percentage of time |
| Control: Sensor-Augmented Pump Therapy | Percent Time Near Normoglycemia | 52 percentage of time |
p-value: =0.037Wilcoxon (Mann-Whitney)
Secondary
Glycemic Events
Number of nights with \>= 1 hypo- and hyperglycemic event occurring overnight during the camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group.
Time frame: 6 nights
Population: Data from OCL nights during which there were technical problems (infusion set failure, sensor error \>20%, pump failure with \>60-min interruption to closed-loop) were removed. Only nights with a minimum of 5h of OCL were included. For control, only data from nights where sensor error was \<20% with a minimum of 5h were included.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Experimental: Closed-Loop Control | Glycemic Events | Hyperglycemic (>250mg/dl) | 4 nights with >= 1 event |
| Experimental: Closed-Loop Control | Glycemic Events | Hypoglycemic (<70mg/dl) | 7 nights with >= 1 event |
| Control: Sensor-Augmented Pump Therapy | Glycemic Events | Hyperglycemic (>250mg/dl) | 4 nights with >= 1 event |
| Control: Sensor-Augmented Pump Therapy | Glycemic Events | Hypoglycemic (<70mg/dl) | 14 nights with >= 1 event |
Secondary
Overnight Glucose
Mean overnight glucose during camp study. Participants were randomized to either closed-loop (experimental) or sensor-augmented pump therapy (control) for the first night and then crossed over every other night to the other therapy over the course of the 5- to 6-day camp session. Thus there were \ 60 nights of data for each intervention. However, data from closed-loop nights during which there were technical problems such as infusion set failure, sensor error \>20%, or pump failure resulting in a \>60-min interruption to closed-loop control were removed to allow for analysis of algorithm performance. Only nights with a minimum of 5 hours of closed-loop were included, and all glucose data were included in the analysis. For comparison, only data from nights during which sensor error was, \<20% with a minimum of 5 hours were included in the control group.
Time frame: 6 nights
Population: Data from OCL nights during which there were technical problems (infusion set failure, sensor error \>20%, pump failure with \>60-min interruption to closed-loop) were removed. Only nights with a minimum of 5h of OCL were included. For control, only data from nights where sensor error was \<20% with a minimum of 5h were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Experimental: Closed-Loop Control | Overnight Glucose | 140 mg/dL | Standard Deviation 18 |
| Control: Sensor-Augmented Pump Therapy | Overnight Glucose | 147 mg/dL | Standard Deviation 36 |
p-value: =0.34Wilcoxon (Mann-Whitney)