This multi-center randomized control trial (RCT) will compare efficacy and safety endpoints using the insulin-only configuration of the iLet Bionic Pancreas (BP) System versus Usual Care (UC) during a 13-week study period. Participants may be enrolled initially into a screening protocol and then transfer into the RCT protocol, or they may enter directly into the RCT protocol. The RCT will be followed by an Extension Phase in which the RCT Usual Care (UC) Group will use the insulin-only configuration of the iLet Bionic Pancreas (BP) System for 3 months. At the completion of use of the BP system in the RCT only, participants will enter a 2-4 day Transition Phase and be randomly assigned to either transition back to their usual mode of therapy (MDI or pump therapy) based on therapeutic guidance from the iLet BP System or transition back to their usual mode of therapy based on what their own insulin regimens were prior to enrolling in the RCT. There is an optional ancillary study to assess the safety of utilizing self-monitored blood glucose (SMBG) measurements instead of continuous glucose monitor (CGM) measurements as input into the iLet for \~48-60 hours. The Study is intended to mirror a real-world situation where CGM may not be available for an extended period of time (eg, user runs out of sensors and is awaiting new shipment).
Primary Objective • To compare the efficacy and safety of the insulin-only configuration of the iLet BP System (using insulin lispro, insulin aspart) the BP System using Fiasp (BPFiasp) \[adults only\]) in maintaining near-normal glycemia relative to usual care in a home-use study in adults and children with T1D. Secondary Objectives • To assess the impact of the insulin-only configuration of the iLet BP System on quality of life and treatment satisfaction. The study has four major parts: (1) the Test-Run Phase, (2) the RCT Period, (3) the Extension Phase for the UC Arm, and (4) the Transition Phase. These four parts are described below, and detailed in the main part of the protocol. A Test-Run Phase will be conducted to (1) test the functionality of all aspects of the iLet BP System, (2) train the clinical staff on the execution of the clinical protocol, and (3) provide hands-on training with the device prior to initiating the RCT Period. The initial test run will be conducted at one site (MGH) with \~5 participants using the iLet BP system for 4-7 days. If there are no safety or consequential device issues, a test run will be conducted at each of the other 15 sites, with \~2 participants per site using the iLet BP system for 4-7 days. The iLet BP system will use insulin lispro or insulin aspart. Results of this Test-Run Phase will be evaluated for safety prior to beginning the RCT Period as described in section 3.3. The 13-week, parallel-group, multi-center RCT Period is designed to compare the insulin-only iLet BP Group using insulin lispro, insulin aspart, or Fiasp (adults only); and a control group following usual care (UC Group). Upon completion of the RCT Period, the BP Group will enter the 2-4 day Transition Phase and the UC Group will enter the Extension Phase. The UC Group Extension Phase will immediately follow the RCT Period. Participants from the UC Group who complete the primary outcome visit, miss no more than 3 of the maximum possible number of the weekly questionnaires, attend all clinic visits, and follow study procedures for collecting CGM data during the RCT Period, will be given the option to use the iLet BP system for 13 weeks. The visit schedule and procedures for the Extension Phase will be similar to that of the BP Group in the RCT Period. A 2-4 day Transition Phase will be conducted for all participants who complete BP use at the end of the RCT Period (BP Group). Participants will be randomly assigned (1:1) to either transition back to their usual mode of therapy (MDI or pump therapy) based on therapeutic guidance from the iLet BP system or transition back to their usual mode of therapy based on what their own insulin regimens were prior to enrolling in the RCT Period. For those randomized to using their pre-study regimens, the dosing can be adjusted by the investigator to mitigate safety issues but should follow pre-study regimen as closely as possible. An optional ancillary study will be offered to participants who are using the iLet at the time of the 13-week randomized trial visit. This will will assess the safety of utilizing blood glucose measurements instead of CGM measurements as input into the iLet for \~48-60 hours. It will be completed at the end of the RCT for those in the BP Group prior to the Transition Phase. Test-Run Visit and Phone Contact Schedule * Screening Visit - Eligibility assessed, informed consent, point-of-care/local HbA1c, testing and procedures similar to the RCT Screening Visit including psychosocial questionnaires; if eligible, BP system started. o For participants who completed the separate screening protocol, eligibility will be reassessed. Point-of-care/local HbA1c will be obtained if more than 28 days have elapsed. Participants will not need to repeat the psychosocial questionnaires. * Phone contact after 1-2 days * Shut-down visit at the end of the study period 4-7 days RCT Period Visit and Phone Contact Schedule * Screening Visit (which may be completed as part of a separate screening protocol) * Eligibility assessed, informed consent signed, point-of-care/local HbA1c, psychosocial questionnaires completed, blinded Dexcom G6 CGM sensor placed for non Dexcom G6 users. * For baseline data collection, participants using a personal Dexcom G6 who have at least 85% of possible glucose data in last 14 days can skip the blinded CGM wear * Participants using a personal Dexcom G6 with \<85% of data will use their personal Dexcom G6. * For participants who completed the separate screening protocol, eligibility will be reassessed. Point-of-care/local HbA1c will be obtained if more than 28 days have elapsed. Participants will not need to repeat the psychosocial questionnaires or blinded CGM wear. * If the separate screening protocol or Test Run Phase of this protocol was completed or blinded CGM wear is not needed, randomization can proceed immediately. If blinded CGM wear was performed as part of this protocol, randomization visit will occur14-21 days after screening. * Prior to randomization, eligibility will be reassessed and blood drawn for central lab HbA1c * BP study start/UC study start on day of Randomization Visit * Phone contacts after 1-2 days and 7 (±2) days * Visits at 2 weeks (±4 days), 6 weeks (±4 days), 10 weeks (±4 days), and \~13 weeks (91-98 days from randomization): * Participants in the UC Group will wear a blinded Dexcom G6 sensor throughout the entire study unless they are current users of the Dexcom G6 CGM, in which case they will continue to use their own Dexcom G6 CGM. * At the 6-week and 13-week visits, central lab HbA1c determination and psychosocial questionnaires UC Group Extension Phase Visit and Phone Contact Schedule * BP initiation at 13-week visit * Phone contacts after 13 weeks plus 1-2 days and 14 weeks (±2 days) * Visits at 15 weeks (± 4 days), 19 (±4 days), 23 (±4 days), and \~26 weeks (182-189 days): * At the 19-week and 26-week visits, central lab HbA1c determination and psychosocial questionnaires Transition Phase Visit Schedule * Randomization and transition to UC regimen at 13-week visit for RCT BP Group for a period of 2-4 days in duration. * Visit ≤4 days later for end of study Ancillary Study Day 1 (13-week visit of the RCT) - stop CGM, start blinded CGM, start SMBG at least every 2 hours during waking hours and at least once during each overnight for the next 48-60hrs. Day 2: Phone call for safety Day 3: stop iLet, stop blinded CGM, restart unblinded CGM, enter Transition Phase.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
440
iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor using lispro or aspart insulin.
iLet Bionic Pancreas System, which consists of an integrated infusion pump, touchscreen display, Bluetooth radio, and insulin dosing algorithms, that automatically controls Fiasp insulin delivery based on glucose values obtained by communicating with a Dexcom G6 sensor.
Using pre-study insulin regimen with the Dexcom G6 CGM
Pre-study insulin delivery method with SMBG and blinded CGM with dosing guidance by the BP
Children's Hospital of Orange County (Pediatrics)
Orange, California, United States
University of California - San Diego (Adults)
San Diego, California, United States
Stanford University (Pediatrics and Adults)
Stanford, California, United States
Barbara Davis Center for Diabetes (Pediatrics and Adults)
Aurora, Colorado, United States
Children's National Health System (Pediatrics)
Washington D.C., District of Columbia, United States
Nemours Children's Clinic (Pediatrics)
Jacksonville, Florida, United States
Emory University (Pediatrics)
Atlanta, Georgia, United States
Massachusetts General Hospital - Diabetes Research Center (Peds and Adults)
Boston, Massachusetts, United States
Henry Ford Health System (Adults)
Detroit, Michigan, United States
Washington University (Adults)
St Louis, Missouri, United States
...and 6 more locations
HbA1c
The primary outcome is superiority for central lab hemoglobin A1c at 13 weeks. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Non-inferiority for CGM-measured Time <54 mg/dL (Key Secondary Endpoint)
The key secondary endpoint is CGM-measured time \<54 mg/dL over 13 weeks
Time frame: 13 weeks
CGM-measured Mean Glucose Level Over 13 Weeks
Time frame: 13 weeks
CGM-measured Percentage Time 70-180 mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-measured Percentage Time >180 mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-measured Percentage Time >250 mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-measured Glucose Standard Deviation (SD) mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-Measured Percentage Time <70 mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-measured Percentage Time <54 mg/dL Over 13 Weeks
Time frame: 13 weeks
CGM-Measured Glucose Coefficient of Variation Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.0%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c \<7.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.0% in Participants With Baseline HbA1c >7.5%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c \<7.0% at week 13 in participants with baseline HbA1c \>7.5%. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c <7.5%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c \<7.5% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c <8.0%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c \<8.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c >9.0%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c \>9.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >0.5%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement \>0.5% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement \>1.0% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c Relative Improvement >10%
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c relative improvement \>10% from baseline to week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: HbA1c Improvement >1.0% or HbA1c <7.0% at 13 Weeks
Other Secondary Efficacy Endpoint: Central lab hemoglobin A1c improvement \>1.0% from baseline to week 13 or central lab hemoglobin A1c \<7.0% at week 13. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-140 mg/dL Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-120 mg/dL Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <60 mg/dL Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Area Over the Curve 70 mg/dL Over 13 Weeks
Area over the curve 70 mg/dL over the 13-week RCT period, measured as the mean of the differences between 70 mg/dL and CGM-measured glucose values below 70 mg/dL. For CGM-measured glucose values above 70 mg/dL, a value of 0 is used instead of the difference. For example, suppose a participant has 10 glucose readings of 78, 60, 59, 71, 80, 100, 110, 115, 120, and 118 mg/dL measured every 5 minutes. The distance between each reading below 70 mg/dL and 70 mg/dL is 0, 10, 11, 0, 0, 0, 0, 0, 0, and 0 mg/dL. The total area is 105 mg/dL\*min; however, this value is then standardized by dividing by the length of time (50 min), resulting in a final CGM-measured area over the curve 70 mg/dL of 2.1 mg/dL.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Low Blood Glucose Index (LBGI)
Other Secondary Efficacy Endpoint: CGM-measured low blood glucose index (LBGI) over 13 weeks. Ranges from 0 to 38.20, with higher values indicating more low CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Hypoglycemic Events
Other Secondary Efficacy Endpoint: CGM-measured hypoglycemic event (at least 15 consecutive minutes with a sensor reading \<54 mg/dL) rate over 13 weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Hyperglycemic Events
Other Secondary Efficacy Endpoint: CGM-measured hyperglycemic event (at least 90 minutes within a 120 minute period with a sensor reading \>300 mg/dL) rate over 13 weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time >300 mg/dL Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Area Under the Curve 180 mg/dL Over 13 Weeks
Area under the curve 180 mg/dL over the 13-week RCT period, measured as the mean of the differences between 180 mg/dL and CGM-measured glucose values above 180 mg/dL. For CGM-measured glucose values under 180 mg/dL, a value of 0 is used instead of the difference. For example, suppose a participant has 10 glucose readings of 100, 120, 182, 200, 250, 193, 179, 150, 140 and 118 mg/dL measured every 5 minutes. The distance between each reading above 180 mg/dL and 180 mg/dL is 0, 0, 2, 20, 70, 13, 0, 0, 0, and 0 mg/dL. The total area is 525 mg/dL\*min; however, this value is then standardized by dividing by the length of time (50 min), resulting in a final CGM-measured area under the curve 180 mg/dL of 10.5 mg/dL.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: High Blood Glucose Index (HBGI)
Other Secondary Efficacy Endpoint: CGM-measured high blood glucose index (HBGI) over 13 weeks. Ranges from 0 to 57.27, with higher values indicating more high CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Mean of Daily Difference in Mean Glucose
Other Secondary Efficacy Endpoint: CGM-measured mean of daily difference in mean glucose over 13 weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time in Range 70-180 mg/dL >70% Over 13 Weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥5%
Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL improvement from baseline to 13 weeks ≥5%
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL Improvement From Baseline to 13 Weeks ≥10%
Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL improvement from baseline to 13 weeks ≥10%
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <70 mg/dL <4%
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: CGM-measured Percentage Time <54 mg/dL <1%
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Blood Glucose Risk Index (LBGI + HBGI)
Other Secondary Efficacy Endpoint: CGM-measured Blood Glucose Risk Index (LBGI + HBGI) over 13 weeks. Calculated as Low Blood Glucose Index (LBGI) + High Blood Glucose Index (HBGI). Ranges from 0 to 57.27, with higher values indicating more low or high CGM-measured glucose values over 13 weeks. Higher values are considered a worse outcome. LBGI and HBGI are inversely related: the presence of a high CGM-measured glucose reading removes an opportunity for a low glucose reading to exist and vice versa, therefore a maximum HBGI of 57.27 and a maximum LGBI of 38.20 cannot exist simultaneously. For instance, if a participant had glucose values of only 401 mg/dL, then the participant has no low glucose values, and therefore their HBGI = 57.27 and LBGI = 0. If a participant had only glucose values of 39 mg/dL, then the participant has no high glucose values, and therefore their HBGI = 0 and LBGI = 38.20. Consequently, the maximum blood glucose risk index is 57.27.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Improvement in HbA1c > 0.5% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without an Increase in HbA1c by > 0.5%
Other Secondary Efficacy Endpoint: Baseline to week 13 improvement in central lab hemoglobin A1c \>0.5% without an increase in CGM-measured percentage time \<54 mg/dl by \>0.5% OR improvement in CGM-measured percentage time \<54 mg/dl by \>0.5% without an increase in central lab hemoglobin A1c by \>0.5%. Glycated Hemoglobin A1C (HbA1c) is a physiological marker of the percentage of red blood cells that have glycated (bonded with a sugar). HbA1c is used to measure changes in average blood sugar over the past three months.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Improvement in Time 70-180 mg/dl by >10% Without an Increase in Time < 54 mg/dl by > 0.5% OR Improvement in Time < 54 mg/dl by > 0.5% Without a Decrease in Time 70-180 mg/dl by > 10%
Other Secondary Efficacy Endpoint: Baseline to 13-week improvement in CGM-measured percentage time 70-180 mg/dL by \>10% without an increase in CGM-measured percentage time \<54 mg/dL by \>0.5% OR improvement in CGM-measured percentage time \<54 mg/dL by \>0.5% without a decrease in CGM-measured percentage time 70-180 mg/dL by \>10%
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Mean Glucose <154 mg/dL and Time <54 mg/dL <1%
Other Secondary Efficacy Endpoint: CGM-measured mean glucose \<154 mg/dL and percentage time \<54 mg/dL \<1% over 13 weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Time in Range 70-180 mg/dL >70% and Time <54 mg/dL <1%
Other Secondary Efficacy Endpoint: CGM-measured percentage time in range 70-180 mg/dL \>70% and percentage time \<54 mg/dL \<1% over 13 weeks
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Total Daily Insulin (Units/kg)
Other Secondary Efficacy Endpoint: Total daily insulin (units/kg) from week 13 site-reported insulin data for the UC group and iLet pump device data over 13 weeks for the BP-A/L and BP-F groups.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Percentage Change in the TDD of Insulin Over the First Two-week Period Relative to the TDD of Insulin in the Last Two-week Period
Other Secondary Efficacy Endpoint: Percentage change in the TDD of insulin over the first two-week period relative to the TDD of insulin in the last two-week period from iLet pump device data over 13 weeks for the BP-A/L and BP-F groups.
Time frame: Weeks 1-2 and weeks 12-13
Other Secondary Efficacy Endpoint: Body Weight at Week 13
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Body Mass Index (BMI) at Week 13
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Mean Participant-reported Number of Hypoglycemic Events Requiring Carbohydrate Treatment Per 24 Hours
Mean participant-reported number of hypoglycemic events requiring carbohydrate treatment per 24 hours, based on the responses to the question, 'How many times in the last 24 hours did you take carbohydrates to treat a low blood sugar?' administered to participants once weekly during the 13-week RCT period.
Time frame: 13 weeks
Other Secondary Efficacy Endpoint: Mean Participant-reported Grams of Carbohydrate Taken Specifically to Prevent or Treat Hypoglycemic Events Per 24 Hours
Mean participant-reported number of hypoglycemic events requiring carbohydrate treatment per 24 hours, based on the responses to the question, 'Estimate the total amount of grams of carbohydrates you were given to treat these low blood sugars', which is a follow-up question to 'How many times in the last 24 hours did you take carbohydrates to treat a low blood sugar?'. Both questions were administered to participants once weekly during the 13-week RCT period.
Time frame: 13 weeks
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