Type1 Diabetes Mellitus
Conditions
Keywords
bionic pancreas, closed loop, insulin, continuous glucose monitor
Brief summary
The iLet is a closed-loop delivery system that can be used in insulin-only, bihormonal, or glucagon-only configurations. Previous studies have utilized a phone-based bionic pancreas. The iLet consists of a touchscreen-enabled, menu-driven user interface and an onboard microprocessor that provides a comprehensive and standalone platform, which allows the iLet to operate independently of smartphones or other devices and without the need for internet support during routine operation. This is a multicenter study of adult participants with type 1 diabetes, who will manage their diabetes with the iLet bionic pancreas compared to usual care.
Detailed description
This study will serve as a transitional study, bridging to larger and longer outpatient pivotal studies using the insulin-only configuration of the bionic pancreas. The Adult RCT Period will consist of a multi-center, three-period, random-order, cross-over, feasibility study in 36 adult participants ≥ 18 years old with T1D. Insulin therapy for each participant will be administered (i) using the iLet in the insulin-only configuration and the insulin analog that they use for their usual care (either Humalog or Novolog) for 7 days, (ii) in another period using the iLet in the insulin-only configuration with faster insulin aspart (Fiasp) for 7 days (iii) in a third period using the participant's own usual care (UC) for 7 days. All three experimental periods will be followed by round-the-clock, remote, telemetric monitoring for hyperglycemia (\> 300 mg/dl for ≥ 90 minutes) and hypoglycemia (\< 50 mg/dl for ≥ 15 minutes). Half the subjects enrolled were expected to manage their diabetes with MDI and the other half with insulin pumps in their UC. An implantable Eversense CGM will also be placed in half the study participants for a CGM comparison.
Interventions
iLet Bionic Pancreas insulin-only configuration with Humalog or Novolog
DRUGiLet Bionic Pancreas insulin-only configuration with Fiasp
iLet Bionic Pancreas insulin-only configuration with Fiasp (faster insulin aspart)
OTHERUsual care
Usual care
Sponsors
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis of type 1 diabetes for at least one year and using insulin for at least 1 year 2. Diabetes managed using an insulin pump for ≥ 3 months or with multiple daily injections (approximately 1/2 of participants should use a pump and approximately 1/2 should use MDI) 3. Age ≥18 years; • There is no upper age limit in the Adult RCT Period (instead the
Exclusion criteria
are used to restrict the participants to those healthy enough to participate in the trial) 4. HbA1c level \<11.0% • A point of care or local lab measurement is used to assess eligibility for screening. 5. At least 3 SMBG meter tests daily on average or use of a CGM and 2 or more SMBG meter tests daily on average by history 6. For females, not currently known to be pregnant • If female, sexually active, and at risk for pregnancy, must agree to use a highly effective form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all women who are post-menarche and pre-menopause who are not surgically sterile. Participants who become pregnant will be discontinued from the study. 7. An understanding of and willingness to follow the protocol and sign the informed consent and assent where applicable
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mean CGM Glucose | Days 3-7 for the RCT Period |
| Percentage of Time Where Glucose is Less Than 54 mg/dL | Days 3-7 for the RCT Period |
Other
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Time Where Glucose is Less Than 70 mg/dL | Days 3-7 for the RCT Period | — |
| Percentage of Time in the Glucose Target Range of 70-180 mg/dl | Days 3-7 for the RCT Period | — |
| Percentage of Time Where Glucose is Greater Than 180 mg/dL | Days 3-7 for the RCT Period | — |
| Percentage of Time Where Glucose is Less Than 60 mg/dL | Days 3-7 for the RCT Period | — |
| Episodes of Severe Hypoglycemia | Days 3-7 for the RCT Period | Pre-specified to report the total number of episodes summed across all participants |
| Percentage Time in the Glucose Target Range of 70-120mg/dL | Days 3-7 for the RCT Period | — |
| Mean Absolute Relative Difference Between Dexcom G5 CGM and Contour Next One Glucose Meter | Days 3-7 for the RCT Period | The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100\*(CGM-reference glucose)/reference glucose |
| Mean Absolute Relative Difference Between Senseonics Eversense CGM and Contour Next One Glucose Meter | Days 1-7 of the Adult RCT period | The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100\*(CGM-reference glucose)/reference glucose |
| Percentage of Time Where Glucose is Greater Than 250 mg/dL | Days 3-7 for the RCT Period | — |
| Episodes of Diabetic Ketoacidosis (DKA) | Days 3-7 for the RCT Period | pre-specified to report the total number of episodes summed across all participants |
Countries
United States
Participant flow
Recruitment details
18 participants were recruited at MGH and 18 participants at Stanford
Pre-assignment details
This study consisted of a test-run period followed by an RCT
Participants by arm
| Arm | Count |
|---|---|
| All Study Participants 36 adult patients with type 1 diabetes will complete 3 arms in a random-order crossover fashion. Participants in the usual care arm (UC) will manage their diabetes with either multiple daily injections or continuous subcutaneous insulin infusion (pump therapy). All subjects will wear Dexcom G5 continuous glucose monitor (CGM) and half of all subjects will also wear a senseonics CGM.
Each arm is 7 days, no washout between arms | 36 |
| Total | 36 |
Baseline characteristics
| Characteristic | All Study Participants | — |
|---|---|---|
| Age, Categorical <=18 years | 0 Participants | — |
| Age, Categorical >=65 years | 3 Participants | — |
| Age, Categorical Between 18 and 65 years | 32 Participants | — |
| Age, Continuous | 41 years STANDARD_DEVIATION 18 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Race/Ethnicity, Customized American Indian/Alaskan Native | 1 Participants | — |
| Race/Ethnicity, Customized Asian | 5 Participants | — |
| Race/Ethnicity, Customized Bklack/African-American | 1 Participants | — |
| Race/Ethnicity, Customized White non-hispanic | 28 Participants | — |
| Region of Enrollment United States | 35 Participants | — |
| Sex: Female, Male Female | 19 Participants | — |
| Sex: Female, Male Male | 17 Participants | — |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 36 | 0 / 36 | 0 / 36 |
| other Total, other adverse events | 4 / 36 | 15 / 36 | 16 / 36 |
| serious Total, serious adverse events | 0 / 36 | 0 / 36 | 1 / 36 |
Outcome results
Primary
Mean CGM Glucose
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Mean CGM Glucose | 144.3 mg/dl | Standard Deviation 9.5 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Mean CGM Glucose | 162 mg/dl | Standard Deviation 26 |
| iLet Using Fiasp Arm | Mean CGM Glucose | 155 mg/dl | Standard Deviation 12 |
Primary
Percentage of Time Where Glucose is Less Than 54 mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care Arm | Percentage of Time Where Glucose is Less Than 54 mg/dL | 0.58 percentage of time |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time Where Glucose is Less Than 54 mg/dL | 0.53 percentage of time |
| iLet Using Fiasp Arm | Percentage of Time Where Glucose is Less Than 54 mg/dL | 0.56 percentage of time |
Other Pre-specified
Episodes of Diabetic Ketoacidosis (DKA)
pre-specified to report the total number of episodes summed across all participants
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care Arm | Episodes of Diabetic Ketoacidosis (DKA) | 0 number of episodes |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Episodes of Diabetic Ketoacidosis (DKA) | 0 number of episodes |
| iLet Using Fiasp Arm | Episodes of Diabetic Ketoacidosis (DKA) | 0 number of episodes |
Other Pre-specified
Episodes of Severe Hypoglycemia
Pre-specified to report the total number of episodes summed across all participants
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Usual Care Arm | Episodes of Severe Hypoglycemia | 0 number of episodes |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Episodes of Severe Hypoglycemia | 0 number of episodes |
| iLet Using Fiasp Arm | Episodes of Severe Hypoglycemia | 1 number of episodes |
Other Pre-specified
Mean Absolute Relative Difference Between Dexcom G5 CGM and Contour Next One Glucose Meter
The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100\*(CGM-reference glucose)/reference glucose
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Mean Absolute Relative Difference Between Dexcom G5 CGM and Contour Next One Glucose Meter | 18.8 MARD (CGMG-meter glucose)/meter glucose) | Standard Deviation 8.2 |
Other Pre-specified
Mean Absolute Relative Difference Between Senseonics Eversense CGM and Contour Next One Glucose Meter
The MARD is calculated as the mean value of individual absolute relative differences (ARD). The ARD is calculated as follows: 100\*(CGM-reference glucose)/reference glucose
Time frame: Days 1-7 of the Adult RCT period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Mean Absolute Relative Difference Between Senseonics Eversense CGM and Contour Next One Glucose Meter | 13.3 MARD: Mean of all [(CGMG - PG)/PG] | Standard Deviation 5 |
Other Pre-specified
Percentage of Time in the Glucose Target Range of 70-180 mg/dl
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Percentage of Time in the Glucose Target Range of 70-180 mg/dl | 73.3 percentage of time | Standard Deviation 7.35 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time in the Glucose Target Range of 70-180 mg/dl | 62.2 percentage of time | Standard Deviation 16.2 |
| iLet Using Fiasp Arm | Percentage of Time in the Glucose Target Range of 70-180 mg/dl | 69.2 percentage of time | Standard Deviation 9.2 |
Other Pre-specified
Percentage of Time Where Glucose is Greater Than 180 mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Percentage of Time Where Glucose is Greater Than 180 mg/dL | 21.8 percentage of time | Standard Deviation 7.6 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time Where Glucose is Greater Than 180 mg/dL | 34.4 percentage of time | Standard Deviation 16.9 |
| iLet Using Fiasp Arm | Percentage of Time Where Glucose is Greater Than 180 mg/dL | 27.96 percentage of time | Standard Deviation 8.9 |
Other Pre-specified
Percentage of Time Where Glucose is Greater Than 250 mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Percentage of Time Where Glucose is Greater Than 250 mg/dL | 3.64 percentage of time | Standard Deviation 3.03 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time Where Glucose is Greater Than 250 mg/dL | 10.42 percentage of time | Standard Deviation 10.43 |
| iLet Using Fiasp Arm | Percentage of Time Where Glucose is Greater Than 250 mg/dL | 7.73 percentage of time | Standard Deviation 4.99 |
Other Pre-specified
Percentage of Time Where Glucose is Less Than 60 mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Percentage of Time Where Glucose is Less Than 60 mg/dL | 1.67 percentage of time | Standard Deviation 0.73 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time Where Glucose is Less Than 60 mg/dL | 1.3 percentage of time | Standard Deviation 1.23 |
| iLet Using Fiasp Arm | Percentage of Time Where Glucose is Less Than 60 mg/dL | 1.19 percentage of time | Standard Deviation 0.93 |
Other Pre-specified
Percentage of Time Where Glucose is Less Than 70 mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Usual Care Arm | Percentage of Time Where Glucose is Less Than 70 mg/dL | 5.09 percentage of time |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage of Time Where Glucose is Less Than 70 mg/dL | 3.2 percentage of time |
| iLet Using Fiasp Arm | Percentage of Time Where Glucose is Less Than 70 mg/dL | 2.7 percentage of time |
Other Pre-specified
Percentage Time in the Glucose Target Range of 70-120mg/dL
Time frame: Days 3-7 for the RCT Period
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Usual Care Arm | Percentage Time in the Glucose Target Range of 70-120mg/dL | 30.65 percentage of time | Standard Deviation 4.17 |
| iLet With Insulin Analogue (Novolog/Humalog) Arm | Percentage Time in the Glucose Target Range of 70-120mg/dL | 25.65 percentage of time | Standard Deviation 12.36 |
| iLet Using Fiasp Arm | Percentage Time in the Glucose Target Range of 70-120mg/dL | 28.24 percentage of time | Standard Deviation 7.98 |