Type 1 Diabetes Mellitus
Conditions
Keywords
Artificial Pancreas (AP), Type 1 Diabetes Mellitus, Insulin Pump, Continuous Glucose Monitor (CGM), Closed Loop Control (CLC), Sensor-Augmented Pump (SAP)
Brief summary
The objective of the study is to assess efficacy and safety of a closed loop system (t:slim X2 with Control-IQ Technology) in a large randomized controlled trial.
Detailed description
After consent is signed, eligibility will be assessed. Eligible participants not currently using an insulin pump and Dexcom CGM with minimum data requirements will initiate a run-in phase of 2 to 8 weeks that will be customized based on whether the participant is already a pump or CGM user. Participants who skip or successfully complete the run-in will be randomly assigned 2:1 to the use of closed-loop control (CLC group) using t:slim X2 with Control-IQ Technology vs. SAP for 6 months.
Interventions
Participants will use the Tandem t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 6 months at home.
Participants will use an insulin pump with no automated insulin delivery and a study CGM (Dexcom G6) for 6 months at home. Pump-users at the time of enrollment will use their personal pump in this arm. Multiple daily injection (MDI) users at the time of enrollment will use a t:slim X2 insulin pump without Control-IQ technology.
Sponsors
Jaeb Center for Health Research
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Tandem Diabetes Care, Inc.
DexCom, Inc.
Roche Diagnostics GmbH
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
A randomized controlled trial of 6 month at home closed loop system vs. sensor-augmented pump.
Eligibility
Sex/Gender
ALL
Age
14 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year. 2. Familiarity and use of a carbohydrate ratio for meal boluses. 3. Age ≥14.0 years old. 4. For females, not currently known to be pregnant. 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 child-bearing 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. 5. For participants \<18 years old, living with one or more parent/legal guardian knowledgeable about emergency procedures for severe hypoglycemia and able to contact the participant in case of an emergency. 6. Willingness to suspend use of any personal CGM for the duration of the clinical trial once the study CGM is in use. 7. Willingness to use a regular insulin pump during the study with no automatic insulin adjustment based on glucose level when assigned to participate in an SAP group 8. Investigator has confidence that the participant can successfully operate all study devices and is capable of adhering to the protocol. 9. Willingness to switch to lispro (Humalog) or aspart (Novolog) if not using already, and to use no other insulin besides lispro (Humalog) or aspart (Novolog) during the study. 10. Total daily insulin dose (TDD) at least 10 U/day. 11. Willingness not to start any new non-insulin glucose-lowering agent during the course of the trial.
Exclusion criteria
1. Concurrent use of any non-insulin glucose-lowering agent other than metformin (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas). 2. Hemophilia or any other bleeding disorder. 3. A condition, which in the opinion of the investigator or designee, would put the participant or study at risk. 4. Participation in another pharmaceutical or device trial at the time of enrollment or during the study. 5. Employed by, or having immediate family members employed by Tandem Diabetes Care, Inc. or TypeZero Technologies, LLC, or having a direct supervisor at place of employment who is also directly involved in conducting the clinical trial (as a study investigator, coordinator, etc.); or having a first-degree relative who is directly involved in conducting the clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time in Target Range | 26 weeks | The primary outcome is time in target range 70-180 mg/dL measured by CGM in CLC group vs. SAP group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BMI | 26 weeks | Body Mass Index (BMI) kg/m\^2 |
| Number of Participants With HbA1c <7.5% at 26 Weeks | 26 weeks | Number of Participants with HbA1c \<7.5% at 26 weeks |
| Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5% | 26 weeks | HbA1c improvement from baseline to 26 weeks \>0.5% |
| Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% | 26 weeks | HbA1c improvement from baseline to 26 weeks \>1.0% |
| HbA1c Relative Improvement From Baseline to 26 Weeks >10% | 26 weeks | HbA1c relative improvement from baseline to 26 weeks \>10% |
| Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks | 26 weeks | HbA1c improvement from baseline to 26 weeks \>1.0% or HbA1c \<7.0% at 26 weeks |
| HFS-II | 26 weeks | For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses. Fear of Hypoglycemia Survey (HFS-II) for adults has a total score that is summed from the two subscale scores (33 items) and ranges from 0 to 132 with higher scores indicating greater degrees of fear of hypoglycemia. The teen survey has a total of 25 items and the range of Total scores is 0 to 100. The parent version of the survey has a total of 26 items with Total scores that range from 0 to 108. |
| Hyperglycemia Avoidance Scale | 26 weeks | Hyperglycemia Avoidance Scale total score is the sum of 21 items rated on a 4 point Likert scale from 0 (never) to 4 (almost always) and ranges from 0 to 84 with a higher score indicating greater degrees of avoiding hyperglycemia. |
| Diabetes Distress Scale | 26 weeks | Diabetes Distress Scale for adults has 28 items rated on a 6 point Likert scale that ranges from 1 (not a problem) to 6 (a very serious problem). The total score is the mean of the sum of responses and ranges from 1 to 6 where a higher score indicates greater degrees of diabetes distress. |
| Hypoglycemia Confidence Scale | 26 weeks | Hypoglycemia Confidence Scale has 20 items which are rated on a 4-point Likert Scale ranging from 1 (not confident at all) to 4 (very confident) with higher scores indicating higher confidence in dealing with hypoglycemia. A single score is computed by calculating the mean of the sum of all items and ranges from 1 to 4. |
| Clarke Hypoglycemia Awareness Scores | 26 weeks | Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness) |
| INSPIRE Survey Scores | 26 weeks | The INSPIRE questionnaire assesses user expectations and experiences with Insulin Delivery Systems: Perceptions, Ideas, Reflections, Expectations (INSPIRE). Survey total scores are computed by calculating the mean of the sum of all item ratings then multiplying the mean by 25 to scale the score to a range from 0 to 100. Higher scores indicate a more positive perception of insulin delivery systems. Items are rated on a 5 point Likert scale ranging from 0 (strongly disagree) to 4 (strongly agree). The Adult survey has 22 items, the Teens/Adolescents survey has 17 items and the Parent survey has 21 items. |
| System Usability Scores (SUS) | 26 weeks | System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability |
| Technology Acceptance Questionnaire | 26 weeks | Technology Acceptance Survey measures the user's perceptions regarding the burdens and the barriers associated with a technology with a higher score indicates increased technology acceptance. There total score uses 37 items with items are rated on a 5 point scale ranging from 1 (strongly disagree) to 5 (strongly agree) for total score range of 37-185. |
| Total Daily Insulin | 26 weeks | Total Daily Insulin (units) |
| Basal:Bolus Insulin Ratio | 26 weeks | Basal:Bolus Insulin Ratio |
| Weight | 26 weeks | Weight (kg) |
| CGM Time Above 180 | 26 weeks | CGM-measured % above 180 mg/dL |
| CGM Mean Glucose | 26 weeks | CGM-measured mean glucose |
| HbA1c at 26 Weeks | 26 weeks | Hemoglobin A1c measured at 26 weeks |
| CGM Time Below 70 | 26 weeks | CGM-measured % below 70 mg/dL |
| CGM Time Below 54 | 26 weeks | CGM-measured % below 54 mg/dL |
| CGM Time in Range 70-140 mg/dL | 26 weeks | CGM-measured % in range 70-140 mg/dL |
| Coefficient of Variability | 26 weeks | CGM measured glucose variability measured with the coefficient of variation (CV) |
| Standard Deviation of CGM | 26 weeks | CGM measured glucose variability measured with the standard deviation (SD) |
| CGM Time Below 60 | 26 weeks | CGM-measured % below 60 mg/dL |
| LBGI | 26 weeks | Low blood glucose index by CGM with higher index indicating higher risk of hypoglycemia. Values \<1 suggest minimal risk. Index of risk of low blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke WL: Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870-1875, 1998) |
| CGM Hypoglycemia Events | 26 weeks | CGM-measured events of at least 15 consecutive minutes \<70mg/dL per week |
| CGM Time >250 | 26 weeks | CGM-measured % \>250 mg/dL |
| CGM Time >300 | 26 weeks | CGM-measured % \>300 mg/dL |
| HBGI | 26 weeks | High blood glucose index by CGM with higher values indicating higher risk of hyperglycemia. Index of risk of high blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Kumar A, Gonder-Frederick L, Clarke WL. Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. Diabetes Technol Ther 2003;5:817-828pmid:14633347) |
| Number of Participants With HbA1c <7.0% at 26 Weeks | 26 weeks | Number of participants HbA1c \<7.0% at 26 weeks |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Severe Hypoglycemia (Per Protocol) | 26 weeks | Severe hypoglycemia (per protocol) |
| Number of Participants With Diabetic Ketoacidosis (Per Protocol) | 26 weeks | Diabetic ketoacidosis (per protocol) |
| Ketone Events Defined as Day With Ketone Level >1.0 mmol/L | 26 weeks | Ketone events defined as day with ketone level \>1.0 mmol/L |
| CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) | 26 weeks | CGM-measured hypoglycemic events (\>15 minutes with glucose concentration \<54 mg/dL) |
| CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) | 26 weeks | CGM-measured hyperglycemic events (\>15 minutes with glucose concentration \>300 mg/dL) |
| Worsening of HbA1c From Baseline to 26 Weeks by >0.5% | 26 weeks | Worsening of HbA1c from baseline to 26 weeks by \>0.5% |
| Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | 26 weeks | Other serious adverse events (SAE) and serious adverse device events (SADE) |
| Adverse Device Effects (ADE) | 26 weeks | Adverse device effects (ADE) |
| Unanticipated Adverse Device Effects (UADE) | 26 weeks | Unanticipated adverse device effects (UADE) |
| Number of Participants With SH Events | 26 weeks | For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group |
| SH Event Rate Per 100 Person-years | 26 weeks | For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate. |
| Number of Participants With DKA Events | 26 weeks | For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated. |
| DKA Event Rate Per 100 Person-years | 26 weeks | For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate. |
| Any Adverse Event Rate Per 100 Person-years | 26 weeks | For this outcome, the adverse event rate per 100 person-years calculated as a rate. |
| BG-measured Hypoglycemic Events (One BG Record <54 mg/dL) | 26 weeks | BG-measured hypoglycemic events (one BG record \<54 mg/dL) |
| BG-measured Hyperglycemic Events (One BG Record >350 mg/dL) | 26 weeks | BG-measured hyperglycemic events (one BG record \>350 mg/dL) |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Closed Loop Control (CLC) Participants randomized to the closed loop control (CLC) arm will use the t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 6 months.
t:slim X2 with Control-IQ Technology & Dexcom G6 CGM: Participants will use the Tandem t:slim X2 with Control-IQ Technology & Dexcom G6 CGM for 6 months at home. | 112 |
| Sensor-Augmented Pump (SAP) Participants randomized to sensor-augmented pump (SAP) will use an insulin pump with no automated insulin delivery and a study CGM (Dexcom G6) for 6 months.
Sensor-augmented pump (SAP): Participants will use an insulin pump with no automated insulin delivery and a study CGM (Dexcom G6) for 6 months at home. Pump-users at the time of enrollment will use their personal pump in this arm. Multiple daily injection (MDI) users at the time of enrollment will use a t:slim X2 insulin pump without Control-IQ technology. | 56 |
| Total | 168 |
Baseline characteristics
| Characteristic | Closed Loop Control (CLC) | Sensor-Augmented Pump (SAP) | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 31 Participants | 17 Participants | 48 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 81 Participants | 39 Participants | 120 Participants |
| Age, Continuous | 33 years STANDARD_DEVIATION 16 | 33 years STANDARD_DEVIATION 17 | 33 years STANDARD_DEVIATION 16 |
| CGM Time in Target Range 70-180 mg/dL | 61 percentage of time STANDARD_DEVIATION 17 | 59 percentage of time STANDARD_DEVIATION 14 | 60 percentage of time STANDARD_DEVIATION 16 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 13 Participants | 5 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 99 Participants | 51 Participants | 150 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 | 3 Participants | 2 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 7 Participants | 1 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 94 Participants | 53 Participants | 147 Participants |
| Region of Enrollment United States | 112 participants | 56 participants | 168 participants |
| Sex: Female, Male Female | 54 Participants | 30 Participants | 84 Participants |
| Sex: Female, Male Male | 58 Participants | 26 Participants | 84 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 112 | 0 / 56 |
| other Total, other adverse events | 12 / 112 | 2 / 56 |
| serious Total, serious adverse events | 4 / 112 | 0 / 56 |
Outcome results
Primary
Time in Target Range
The primary outcome is time in target range 70-180 mg/dL measured by CGM in CLC group vs. SAP group.
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Time in Target Range | 71 percentage of time | Standard Deviation 12 |
| Sensor-Augmented Pump (SAP) | Time in Target Range | 59 percentage of time | Standard Deviation 14 |
p-value: <0.001Mixed Models Analysis
Secondary
Basal:Bolus Insulin Ratio
Basal:Bolus Insulin Ratio
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Basal:Bolus Insulin Ratio | 1.1 ratio | Standard Deviation 0.7 |
| Sensor-Augmented Pump (SAP) | Basal:Bolus Insulin Ratio | 1.1 ratio | Standard Deviation 0.8 |
Secondary
BMI
Body Mass Index (BMI) kg/m\^2
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | BMI | 26.2 kg/m^2 | Standard Deviation 4.9 |
| Sensor-Augmented Pump (SAP) | BMI | 26.1 kg/m^2 | Standard Deviation 6.1 |
Secondary
CGM Hypoglycemia Events
CGM-measured events of at least 15 consecutive minutes \<70mg/dL per week
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Hypoglycemia Events | 3.3 events per week | Standard Deviation 2.1 |
| Sensor-Augmented Pump (SAP) | CGM Hypoglycemia Events | 4.3 events per week | Standard Deviation 2.7 |
Secondary
CGM Mean Glucose
CGM-measured mean glucose
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Mean Glucose | 156 mg/dL | Standard Deviation 19 |
| Sensor-Augmented Pump (SAP) | CGM Mean Glucose | 170 mg/dL | Standard Deviation 25 |
p-value: <0.001Mixed Models Analysis
Secondary
CGM Time >250
CGM-measured % \>250 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time >250 | 7 percentage | Standard Deviation 6.7 |
| Sensor-Augmented Pump (SAP) | CGM Time >250 | 12.3 percentage | Standard Deviation 10.2 |
Secondary
CGM Time >300
CGM-measured % \>300 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time >300 | 2.4 percentage | Standard Deviation 3.4 |
| Sensor-Augmented Pump (SAP) | CGM Time >300 | 4.6 percentage | Standard Deviation 6 |
Secondary
CGM Time Above 180
CGM-measured % above 180 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time Above 180 | 27 percentage | Standard Deviation 12 |
| Sensor-Augmented Pump (SAP) | CGM Time Above 180 | 38 percentage | Standard Deviation 15 |
p-value: <0.001Mixed Models Analysis
Secondary
CGM Time Below 54
CGM-measured % below 54 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time Below 54 | 0.29 percentage | Standard Deviation 0.29 |
| Sensor-Augmented Pump (SAP) | CGM Time Below 54 | 0.35 percentage | Standard Deviation 0.32 |
p-value: 0.02Mixed Models Analysis
Secondary
CGM Time Below 60
CGM-measured % below 60 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time Below 60 | 0.58 percentage | Standard Deviation 0.52 |
| Sensor-Augmented Pump (SAP) | CGM Time Below 60 | 0.75 percentage | Standard Deviation 0.61 |
Secondary
CGM Time Below 70
CGM-measured % below 70 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time Below 70 | 1.58 percentage | Standard Deviation 1.15 |
| Sensor-Augmented Pump (SAP) | CGM Time Below 70 | 2.25 percentage | Standard Deviation 1.46 |
p-value: <0.001Mixed Models Analysis
Secondary
CGM Time in Range 70-140 mg/dL
CGM-measured % in range 70-140 mg/dL
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | CGM Time in Range 70-140 mg/dL | 46 percentage | Standard Deviation 12 |
| Sensor-Augmented Pump (SAP) | CGM Time in Range 70-140 mg/dL | 36 percentage | Standard Deviation 12 |
Secondary
Clarke Hypoglycemia Awareness Scores
Clarke Hypoglycemia Awareness Scores (0-7 score with higher scores associated with impaired awareness)
Time frame: 26 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Closed Loop Control (CLC) | Clarke Hypoglycemia Awareness Scores | 1 score on a scale |
| Sensor-Augmented Pump (SAP) | Clarke Hypoglycemia Awareness Scores | 2 score on a scale |
Secondary
Coefficient of Variability
CGM measured glucose variability measured with the coefficient of variation (CV)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Coefficient of Variability | 34 percentage SD of Mean | Standard Deviation 5 |
| Sensor-Augmented Pump (SAP) | Coefficient of Variability | 36 percentage SD of Mean | Standard Deviation 5 |
Secondary
Diabetes Distress Scale
Diabetes Distress Scale for adults has 28 items rated on a 6 point Likert scale that ranges from 1 (not a problem) to 6 (a very serious problem). The total score is the mean of the sum of responses and ranges from 1 to 6 where a higher score indicates greater degrees of diabetes distress.
Time frame: 26 weeks
Population: Total Score at 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Diabetes Distress Scale | 1.7 score on a scale | Standard Deviation 0.6 |
| Sensor-Augmented Pump (SAP) | Diabetes Distress Scale | 1.9 score on a scale | Standard Deviation 0.8 |
Secondary
HbA1c at 26 Weeks
Hemoglobin A1c measured at 26 weeks
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | HbA1c at 26 Weeks | 7.06 percentage | Standard Deviation 0.79 |
| Sensor-Augmented Pump (SAP) | HbA1c at 26 Weeks | 7.39 percentage | Standard Deviation 0.92 |
p-value: 0.001Mixed Models Analysis
Secondary
HbA1c Relative Improvement From Baseline to 26 Weeks >10%
HbA1c relative improvement from baseline to 26 weeks \>10%
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | HbA1c Relative Improvement From Baseline to 26 Weeks >10% | 21 percentage | Standard Deviation 19 |
| Sensor-Augmented Pump (SAP) | HbA1c Relative Improvement From Baseline to 26 Weeks >10% | 2 percentage | Standard Deviation 4 |
Secondary
HBGI
High blood glucose index by CGM with higher values indicating higher risk of hyperglycemia. Index of risk of high blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Kumar A, Gonder-Frederick L, Clarke WL. Algorithmic evaluation of metabolic control and risk of severe hypoglycemia in type 1 and type 2 diabetes using self-monitoring blood glucose data. Diabetes Technol Ther 2003;5:817-828pmid:14633347)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | HBGI | 6.3 index | Standard Deviation 3.1 |
| Sensor-Augmented Pump (SAP) | HBGI | 9.0 index | Standard Deviation 4.4 |
Secondary
HFS-II
For adults, teens and parents items on this survey are rated on a 5 point Likert scale from never (0) to almost always (4). The survey is scored by summing item responses. Fear of Hypoglycemia Survey (HFS-II) for adults has a total score that is summed from the two subscale scores (33 items) and ranges from 0 to 132 with higher scores indicating greater degrees of fear of hypoglycemia. The teen survey has a total of 25 items and the range of Total scores is 0 to 100. The parent version of the survey has a total of 26 items with Total scores that range from 0 to 108.
Time frame: 26 weeks
Population: Total Score at 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | HFS-II | 33 score on a scale | Standard Deviation 12 |
| Sensor-Augmented Pump (SAP) | HFS-II | 38 score on a scale | Standard Deviation 18 |
| CLC in Teens | HFS-II | 32 score on a scale | Standard Deviation 10 |
| SAP in Teens | HFS-II | 31 score on a scale | Standard Deviation 16 |
| Parent of Teen in CLC | HFS-II | 33 score on a scale | Standard Deviation 14 |
| Parent of a Teen in SAP | HFS-II | 36 score on a scale | Standard Deviation 15 |
Secondary
Hyperglycemia Avoidance Scale
Hyperglycemia Avoidance Scale total score is the sum of 21 items rated on a 4 point Likert scale from 0 (never) to 4 (almost always) and ranges from 0 to 84 with a higher score indicating greater degrees of avoiding hyperglycemia.
Time frame: 26 weeks
Population: Total Score at 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Hyperglycemia Avoidance Scale | 39 score on a scale | Standard Deviation 7 |
| Sensor-Augmented Pump (SAP) | Hyperglycemia Avoidance Scale | 37 score on a scale | Standard Deviation 11 |
Secondary
Hypoglycemia Confidence Scale
Hypoglycemia Confidence Scale has 20 items which are rated on a 4-point Likert Scale ranging from 1 (not confident at all) to 4 (very confident) with higher scores indicating higher confidence in dealing with hypoglycemia. A single score is computed by calculating the mean of the sum of all items and ranges from 1 to 4.
Time frame: 26 weeks
Population: First two items on hypoglycemia confidence scale
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Closed Loop Control (CLC) | Hypoglycemia Confidence Scale | Execise | 2.3 score on a scale |
| Closed Loop Control (CLC) | Hypoglycemia Confidence Scale | Sleeping | 2.3 score on a scale |
| Sensor-Augmented Pump (SAP) | Hypoglycemia Confidence Scale | Execise | 1.9 score on a scale |
| Sensor-Augmented Pump (SAP) | Hypoglycemia Confidence Scale | Sleeping | 1.9 score on a scale |
Secondary
INSPIRE Survey Scores
The INSPIRE questionnaire assesses user expectations and experiences with Insulin Delivery Systems: Perceptions, Ideas, Reflections, Expectations (INSPIRE). Survey total scores are computed by calculating the mean of the sum of all item ratings then multiplying the mean by 25 to scale the score to a range from 0 to 100. Higher scores indicate a more positive perception of insulin delivery systems. Items are rated on a 5 point Likert scale ranging from 0 (strongly disagree) to 4 (strongly agree). The Adult survey has 22 items, the Teens/Adolescents survey has 17 items and the Parent survey has 21 items.
Time frame: 26 weeks
Population: Scores are measured at 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | INSPIRE Survey Scores | 87 score on a scale | Standard Deviation 14 |
| Sensor-Augmented Pump (SAP) | INSPIRE Survey Scores | 86 score on a scale | Standard Deviation 13 |
| CLC in Teens | INSPIRE Survey Scores | 87 score on a scale | Standard Deviation 13 |
| SAP in Teens | INSPIRE Survey Scores | 74 score on a scale | Standard Deviation 12 |
| Parent of Teen in CLC | INSPIRE Survey Scores | 87 score on a scale | Standard Deviation 13 |
| Parent of a Teen in SAP | INSPIRE Survey Scores | 76 score on a scale | Standard Deviation 12 |
Secondary
LBGI
Low blood glucose index by CGM with higher index indicating higher risk of hypoglycemia. Values \<1 suggest minimal risk. Index of risk of low blood glucose excursion based on a standard formula for non-linear transformation of the blood glucose scale (Kovatchev BP, Cox DJ, Gonder-Frederick LA, Young-Hyman D, Schlundt D, Clarke WL: Assessment of risk for severe hypoglycemia among adults with IDDM: validation of the low blood glucose index. Diabetes Care 21:1870-1875, 1998)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | LBGI | 0.51 units on a scale | Standard Deviation 0.29 |
| Sensor-Augmented Pump (SAP) | LBGI | 0.65 units on a scale | Standard Deviation 0.35 |
Secondary
Number of Participants With HbA1c <7.0% at 26 Weeks
Number of participants HbA1c \<7.0% at 26 weeks
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With HbA1c <7.0% at 26 Weeks | 52 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With HbA1c <7.0% at 26 Weeks | 17 Participants |
Secondary
Number of Participants With HbA1c <7.5% at 26 Weeks
Number of Participants with HbA1c \<7.5% at 26 weeks
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With HbA1c <7.5% at 26 Weeks | 79 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With HbA1c <7.5% at 26 Weeks | 33 Participants |
Secondary
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5%
HbA1c improvement from baseline to 26 weeks \>0.5%
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5% | 35 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >0.5% | 6 Participants |
Secondary
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0%
HbA1c improvement from baseline to 26 weeks \>1.0%
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% | 12 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% | 0 Participants |
Secondary
Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks
HbA1c improvement from baseline to 26 weeks \>1.0% or HbA1c \<7.0% at 26 weeks
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks | 59 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With HbA1c Improvement From Baseline to 26 Weeks >1.0% or HbA1c <7.0% at 26 Weeks | 17 Participants |
Secondary
Standard Deviation of CGM
CGM measured glucose variability measured with the standard deviation (SD)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Standard Deviation of CGM | 53 mg/dL | Standard Deviation 12 |
| Sensor-Augmented Pump (SAP) | Standard Deviation of CGM | 62 mg/dL | Standard Deviation 13 |
Secondary
System Usability Scores (SUS)
System Usability Scores (SUS)-composite score from 0 to 100 with higher scores indicate better perceived usability
Time frame: 26 weeks
Population: Administered to CLC group only. Results from 26-week.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | System Usability Scores (SUS) | 87 score on a scale | Standard Deviation 12 |
Secondary
Technology Acceptance Questionnaire
Technology Acceptance Survey measures the user's perceptions regarding the burdens and the barriers associated with a technology with a higher score indicates increased technology acceptance. There total score uses 37 items with items are rated on a 5 point scale ranging from 1 (strongly disagree) to 5 (strongly agree) for total score range of 37-185.
Time frame: 26 weeks
Population: Administered to CLC arm only. Result from 26-weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Technology Acceptance Questionnaire | 155 score on a scale | Standard Deviation 19 |
Secondary
Total Daily Insulin
Total Daily Insulin (units)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Total Daily Insulin | 55 units | Standard Deviation 27 |
| Sensor-Augmented Pump (SAP) | Total Daily Insulin | 51 units | Standard Deviation 20 |
Secondary
Weight
Weight (kg)
Time frame: 26 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Closed Loop Control (CLC) | Weight | 78.7 kilograms | Standard Deviation 17 |
| Sensor-Augmented Pump (SAP) | Weight | 76.0 kilograms | Standard Deviation 18.9 |
Other Pre-specified
Adverse Device Effects (ADE)
Adverse device effects (ADE)
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Adverse Device Effects (ADE) | 11 Participants |
| Sensor-Augmented Pump (SAP) | Adverse Device Effects (ADE) | 0 Participants |
Other Pre-specified
Any Adverse Event Rate Per 100 Person-years
For this outcome, the adverse event rate per 100 person-years calculated as a rate.
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | Any Adverse Event Rate Per 100 Person-years | 30.2 events per 100 person-yr |
| Sensor-Augmented Pump (SAP) | Any Adverse Event Rate Per 100 Person-years | 7.1 events per 100 person-yr |
Other Pre-specified
BG-measured Hyperglycemic Events (One BG Record >350 mg/dL)
BG-measured hyperglycemic events (one BG record \>350 mg/dL)
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | BG-measured Hyperglycemic Events (One BG Record >350 mg/dL) | 243 days |
| Sensor-Augmented Pump (SAP) | BG-measured Hyperglycemic Events (One BG Record >350 mg/dL) | 181 days |
Other Pre-specified
BG-measured Hypoglycemic Events (One BG Record <54 mg/dL)
BG-measured hypoglycemic events (one BG record \<54 mg/dL)
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | BG-measured Hypoglycemic Events (One BG Record <54 mg/dL) | 129 days |
| Sensor-Augmented Pump (SAP) | BG-measured Hypoglycemic Events (One BG Record <54 mg/dL) | 72 days |
Other Pre-specified
CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL)
CGM-measured hyperglycemic events (\>15 minutes with glucose concentration \>300 mg/dL)
Time frame: 26 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Closed Loop Control (CLC) | CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) | 1.2 events per week |
| Sensor-Augmented Pump (SAP) | CGM-measured Hyperglycemic Events (>15 Minutes With Glucose Concentration >300 mg/dL) | 2.7 events per week |
Other Pre-specified
CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL)
CGM-measured hypoglycemic events (\>15 minutes with glucose concentration \<54 mg/dL)
Time frame: 26 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Closed Loop Control (CLC) | CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) | 0.4 events per week |
| Sensor-Augmented Pump (SAP) | CGM-measured Hypoglycemic Events (>15 Minutes With Glucose Concentration <54 mg/dL) | 0.5 events per week |
Other Pre-specified
DKA Event Rate Per 100 Person-years
For this outcome, the diabetic ketoacidosis event rate per 100 person-years will be calculated as a rate.
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | DKA Event Rate Per 100 Person-years | 1.8 rate per 100 person-years |
| Sensor-Augmented Pump (SAP) | DKA Event Rate Per 100 Person-years | 0 rate per 100 person-years |
Other Pre-specified
Ketone Events Defined as Day With Ketone Level >1.0 mmol/L
Ketone events defined as day with ketone level \>1.0 mmol/L
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | Ketone Events Defined as Day With Ketone Level >1.0 mmol/L | 14 days |
| Sensor-Augmented Pump (SAP) | Ketone Events Defined as Day With Ketone Level >1.0 mmol/L | 15 days |
Other Pre-specified
Number of Participants With Diabetic Ketoacidosis (Per Protocol)
Diabetic ketoacidosis (per protocol)
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With Diabetic Ketoacidosis (Per Protocol) | 1 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With Diabetic Ketoacidosis (Per Protocol) | 0 Participants |
Other Pre-specified
Number of Participants With DKA Events
For this outcome, number of participants with diabetic ketoacidosis (DKA) will be tabulated.
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With DKA Events | 1 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With DKA Events | 0 Participants |
Other Pre-specified
Number of Participants With Severe Hypoglycemia (Per Protocol)
Severe hypoglycemia (per protocol)
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With Severe Hypoglycemia (Per Protocol) | 0 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With Severe Hypoglycemia (Per Protocol) | 0 Participants |
Other Pre-specified
Number of Participants With SH Events
For this outcome, mean +/- SD or summary statistics appropriate to the distribution will be tabulated by treatment group
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Number of Participants With SH Events | 0 Participants |
| Sensor-Augmented Pump (SAP) | Number of Participants With SH Events | 0 Participants |
Other Pre-specified
Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE)
Other serious adverse events (SAE) and serious adverse device events (SADE)
Time frame: 26 weeks
Population: Other Serious Adverse Events that do not include DKA or Severe Hypoglycemia
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Closed Loop Control (CLC) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Concussion | 1 participants |
| Closed Loop Control (CLC) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Otitis | 1 participants |
| Closed Loop Control (CLC) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Cardiac Bypass Surgery | 1 participants |
| Sensor-Augmented Pump (SAP) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Concussion | 0 participants |
| Sensor-Augmented Pump (SAP) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Otitis | 0 participants |
| Sensor-Augmented Pump (SAP) | Other Serious Adverse Events (SAE) and Serious Adverse Device Events (SADE) | Cardiac Bypass Surgery | 0 participants |
Other Pre-specified
SH Event Rate Per 100 Person-years
For this outcome, severe hypoglycemia event rate per 100 person-years will be calculated as a rate.
Time frame: 26 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | SH Event Rate Per 100 Person-years | 0 rate per 100 person-years |
| Sensor-Augmented Pump (SAP) | SH Event Rate Per 100 Person-years | 0 rate per 100 person-years |
Other Pre-specified
Unanticipated Adverse Device Effects (UADE)
Unanticipated adverse device effects (UADE)
Time frame: 26 weeks
Population: Study Device
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Closed Loop Control (CLC) | Unanticipated Adverse Device Effects (UADE) | 1 Unanticipated Adverse Device Effects |
| Sensor-Augmented Pump (SAP) | Unanticipated Adverse Device Effects (UADE) | 0 Unanticipated Adverse Device Effects |
Other Pre-specified
Worsening of HbA1c From Baseline to 26 Weeks by >0.5%
Worsening of HbA1c from baseline to 26 weeks by \>0.5%
Time frame: 26 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Closed Loop Control (CLC) | Worsening of HbA1c From Baseline to 26 Weeks by >0.5% | 8 Participants |
| Sensor-Augmented Pump (SAP) | Worsening of HbA1c From Baseline to 26 Weeks by >0.5% | 5 Participants |