Type 1 Diabetes
Conditions
Keywords
Continuous Glucose Monitor (CGM), Continuous subcutaneous insulin infusion (CSII), Closed Loop Control (CLC), Hybrid Closed Loop (HCL), High-intensity interval training (HIIT), Bolus Priming System (BPS), Fully Automated Closed Loop (FCL), Artificial Pancreas (AP)
Brief summary
The purpose of this study is to understand the impact of the automated priming boluses on the safety and feasibility of a new fully automated AP controller.
Detailed description
Study participants will be admitted to the hotel for a 4-night study, receiving the two sessions in random order: 1) Fully control loop (FCL) with the bolus priming system (BPS) activated, 2) FCL without the BPS, with a 24-hour washout period in between. During the admission, participants will receive structured meals and have blood glucose control followed to compare time in range 70-180 mg/dL between Controller sessions. After the first 24 hour period on the first FCL approach (BPS vs. no BPS,) that the participant has been randomized to, there will be a 24 hour challenge period before shifting to the other randomized approach; during this session participants will undergo further testing of the control algorithm, including meal challenges and a high-intensity interval training bout.
Interventions
DEVICEFCL+BPS
The automated insulin delivery system includes the Bolus Priming System, a software automatically analyzing past continuous glucose monitoring values to trigger priming insulin bolus delivery isn the suspected presence of meal like glycemic disturbances
DEVICEFCL
The automated insulin delivery system does not include the Bolus Priming System, and therefore does not automatically command priming boluses.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Marc Breton
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
Participants will be randomized to the order that they experience the use of the Bolus Priming System (BPS) in fully automated closed loop (FCL) (for 24 hours each, with a 24-hour challenge period in between): 1) with the BPS active, 2) BPS inactive.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age ≥18.0 and ≤65 years old at time of consent 2. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year 3. Currently using insulin for at least six months 4. Currently using insulin pump for at least three months 5. Using insulin parameters such as carbohydrate ratio and correction factors consistently on their pump in order to dose insulin for meals or corrections 6. Current regular exercise (e.g. walk, bike, jog) and be able to participate in a high intensity interval training activity. 7. Access to internet and willingness to upload data during the study as needed 8. For females, not currently known to be pregnant or breastfeeding 9. If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative serum or urine pregnancy test will be required for all females of childbearing potential. Participants who become pregnant will be discontinued from the study. Also, participants who during the study develop and express the intention to become pregnant within the timespan of the study will be discontinued. 10. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use 11. Willingness to use the UVa closed-loop system throughout study admission 12. Willingness to use personal lispro (Humalog) or aspart (Novolog) during the study admission. 13. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial (including metformin/biguanides, GLP-1 receptor agonists, pramlintide, DPP-4 inhibitors, sulfonylureas and naturaceuticals) 14. Willingness to eat at least 1 g/kg of carbohydrate per day during the hotel admission 15. Willingness to reschedule if placed on oral steroids 16. An understanding and willingness to follow the protocol and signed informed consent 17. Willingness to follow COVID-19 protocols in place at the time of study.
Exclusion criteria
1. History of diabetic ketoacidosis (DKA) in the 6 months prior to enrollment 2. Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment 3. Pregnancy or intent to become pregnant during the trial 4. Currently being treated for a seizure disorder 5. Planned surgery during study duration. 6. Treatment with meglitinides/sulfonylureas at the time of hotel study. 7. Use of metformin/biguanides, GLP-1 agonists, pramlintide, DPP-4 inhibitors, SGLT-2 inhibitors, or naturaceuticals with a change in dose in the past month. 8. Coronary artery disease or heart failure, unless written clearance is received from a cardiologist or personal health care provider allowing clearance for high-intensity interval training and documentation of a negative stress test within the year 9. History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted or previous ablation of arrhythmia without recurrence which may be permitted) 10. Clinically significant electrocardiogram (ECG) at time of Screening, as interpreted by the study medical physician. 11. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples: 1. Inpatient psychiatric treatment in the past 6 months 2. Presence of a known adrenal disorder 3. Abnormal liver function test results (Transaminase \>2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function 4. Uncontrolled thyroid disease 5. Musculoskeletal or other condition that limits participation in exercise portion of study 12. A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol. 13. Positive Covid-19 test result
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Daytime Percent Time-in-range | 18 hours | Percentage of CGM values falling between 70 and 180 mg/dL during daytime (6am to midnight) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Difference in Overall Percent Time-in-range | 24 hours | Percentage of CGM values falling between 70 and 180 mg/dL |
| Difference in Daytime Percent Time-below-range | 18 hours | Percentage of CGM values falling below 70mg/dL during daytime (6am to midnight) |
| Difference in Overall Percent Time-below-range | 24 hours | Percentage of CGM values falling below 70mg/dL |
Countries
United States
Participant flow
Pre-assignment details
15 participants signed informed consent for the main study. 2 screen failed and 2 withdrew prior to randomization to arms. Results reported on 11 participants who were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Full Closed-loop (FCL) With Bolus Priming System (BPS) Followed by FCL Without BPS Two separate 24-hour periods during where fully closed loop (FCL) control is used with & without the Bolus Priming system (BPS) active (BPS is designed to recognize meal ingestion & deliver a quick priming dose of insulin prior to extreme blood sugar excursions.) These will be separated by a 24-hour challenge period which will involve further meal & exercise challenges. During these 24-hour periods, participants will be followed for the experimental meals as part of the Study Controller Sessions to compare blood glucose control with & without the BPS. The study meals & activities will be standardized between study sessions.
During a washout period, we will test the RocketAP system in FCL with further challenges:
* A session of high-intensity interval training
* A high-carbohydrate, high-fat meal
* Ingestion of a bolus of simple sugar
FCL+BPS: The automated insulin delivery system includes the Bolus Priming System, a software automatically analyzing past continuous glucose monitoring values to trigger priming insulin bolus delivery isn the suspected presence of meal like glycemic disturbances
FCL: The automated insulin delivery system does not include the Bolus Priming System, and therefore does not automatically command priming boluses. | 6 |
| Full Closed-loop (FCL) Without Bolus Priming System (BPS) Followed by FCL With BPS Two separate 24-hour periods during where fully closed loop (FCL) control is used with & without the Bolus Priming system (BPS) active (BPS is designed to recognize meal ingestion & deliver a quick priming dose of insulin prior to extreme blood sugar excursions.) These will be separated by a 24-hour challenge period which will involve further meal & exercise challenges. During these 24-hour periods, participants will be followed for the experimental meals as part of the Study Controller Sessions to compare blood glucose control with & without the BPS. The study meals & activities will be standardized between study sessions.
During a washout period, we will test the RocketAP system in FCL with further challenges:
* A session of high-intensity interval training
* A high-carbohydrate, high-fat meal
* Ingestion of a bolus of simple sugar
FCL+BPS: The automated insulin delivery system includes the Bolus Priming System, a software automatically analyzing past continuous glucose monitoring values to trigger priming insulin bolus delivery isn the suspected presence of meal like glycemic disturbances
FCL: The automated insulin delivery system does not include the Bolus Priming System, and therefore does not automatically command priming boluses. | 5 |
| Total | 11 |
Baseline characteristics
| Characteristic | Full Closed-loop (FCL) With Bolus Priming System (BPS) Followed by FCL Without BPS | Full Closed-loop (FCL) Without Bolus Priming System (BPS) Followed by FCL With BPS | Total |
|---|---|---|---|
| Age, Continuous | 33.8 years STANDARD_DEVIATION 11.7 | 43.8 years STANDARD_DEVIATION 14.9 | 38.4 years STANDARD_DEVIATION 13.6 |
| Baseline Hemoglobin A1c | 6.3 percentage of glycosylated hemoglobin STANDARD_DEVIATION 0.9 | 7.2 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.3 | 6.7 percentage of glycosylated hemoglobin STANDARD_DEVIATION 1.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 5 Participants | 11 Participants |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 11 |
| other Total, other adverse events | 0 / 11 | 1 / 11 |
| serious Total, serious adverse events | 0 / 11 | 0 / 11 |
Outcome results
Primary
Difference in Daytime Percent Time-in-range
Percentage of CGM values falling between 70 and 180 mg/dL during daytime (6am to midnight)
Time frame: 18 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FCL With BPS | Difference in Daytime Percent Time-in-range | 67.4 percentage of CGM values | Standard Deviation 15.1 |
| FCL Without BPS | Difference in Daytime Percent Time-in-range | 65.1 percentage of CGM values | Standard Deviation 18.5 |
p-value: 0.429195% CI: [-3.8, 8.3]t-test, 2 sided
Secondary
Difference in Daytime Percent Time-below-range
Percentage of CGM values falling below 70mg/dL during daytime (6am to midnight)
Time frame: 18 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FCL With BPS | Difference in Daytime Percent Time-below-range | 0 percentage of CGM values |
| FCL Without BPS | Difference in Daytime Percent Time-below-range | 0 percentage of CGM values |
Secondary
Difference in Overall Percent Time-below-range
Percentage of CGM values falling below 70mg/dL
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| FCL With BPS | Difference in Overall Percent Time-below-range | 0 percentage of CGM values |
| FCL Without BPS | Difference in Overall Percent Time-below-range | 0 percentage of CGM values |
Secondary
Difference in Overall Percent Time-in-range
Percentage of CGM values falling between 70 and 180 mg/dL
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| FCL With BPS | Difference in Overall Percent Time-in-range | 74.3 percentage of CGM values | Standard Deviation 13.6 |
| FCL Without BPS | Difference in Overall Percent Time-in-range | 73.1 percentage of CGM values | Standard Deviation 16.2 |