Diabetes Mellitus, Type 1
Conditions
Keywords
Closed-Loop Control (CLC), Sensor-Augmented Therapy (SAP), USS Virginia, Continuous Glucose Monitor (CGM), Insulin Pump, Artificial Pancreas (AP)
Brief summary
The purpose of this study is to use an investigational type of technology called Closed-Loop Control (CLC) Medical Platform System to help control blood sugar in people with type 1 diabetes mellitus in a home setting.
Detailed description
The CLC is an artificial pancreas (AP) application that uses advanced closed loop control algorithms to automatically manage blood glucose levels for people with Type 1 Diabetes. The system modulates insulin to keep blood glucose in a targeted range. The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive.These functionalities occur in a randomized cross-over design, each occurring for 8 weeks. These modalities are: 1. SAP=sensor-augmented pump only 2. USS+SAP (d)= Evening and Overnight Closed-Loop Control=SAP during day and CLC starting at dinner and continuing overnight 3. USS+CLC (d)= 24/7 Closed-Loop Control=24-hour Day and Night Closed Loop Control
Interventions
DEVICECLC
The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Roche Diagnostic Ltd.
TypeZero Technologies, LLC
Tandem Diabetes Care, Inc.
DexCom, Inc.
University of Virginia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* type 1 diabetes for at least one year * using insulin for at least 1 year * an insulin pump for at least 6 months * willingness to switch to lispro (Humalog) or aspart (Novolog) if using glulisine (Apidra).
Exclusion criteria
* a medical condition or being been treated with medications that might interfere with the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time <70 mg/dl by CGM | 8 weeks | Overnight CLC achieved by USS+SAP(d) (also known at Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c \< 7.5% vs ≥7.5% and time of day. |
| Hemoglobin A1c | 8 weeks | Overnight CLC achieved by USS+SAP(d) (also known as Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c \< 7.5% vs ≥7.5% and time of day. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hemoglobin A1c by Study Session | 8 weeks | Hemoglobin A1c after each 8 weeks study session by Group A and Group B. |
| Time >180 mg/dL by CGM | 8 weeks | Time in hyperglycemia range \>180 mg/dL measured by CGM |
| Time Between 70-180 mg/dL by CGM | 8 weeks | Time in target range 70-180 mg/dL measured by CGM |
| Low Blood Glucose Index (LBGI) | 8 weeks | Index measure of low blood glucose risk. This is an index that indicates risk of hypoglycemia with low values indicating lower risk of hypoglycemia (particularly values 1 or lower). |
| High Blood Glucose Index (HBGI) | 8 weeks | Index measure of high blood glucose risk. |
| Mean Glucose by CGM | 8 weeks | Mean glucose measured by CGM overall in mmol/L |
| CGM <70mg/dL | 8 weeks | Percentage time \<70mg/dL measured by CGM in three study phases combining Group A and B. |
Countries
United States
Participant flow
Pre-assignment details
103 participants signed informed consent and were assessed for eligibility.10 were excluded prior to randomization (7 did not meet inclusion criteria, 2 declined to participate, 1 lost to followup). 93 participants were randomized and assigned to groups.
Participants by arm
| Arm | Count |
|---|---|
| Group A Order of intervention will be 1) SAP; 2) USS + SAP(d); 3) USS +CLC (d); 4) USS + SAP(d)
CLC: The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive. | 40 |
| Group B Order of intervention will be 1)USS + SAP(d) ; 2)USS +CLC (d); 3) USS + SAP(d); 4) SAP
CLC: The CLC will be deployed with different functionalities at different stages of the trial, resulting in variation in what the subject will be responsible for and what the system will drive. | 40 |
| Total | 80 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1: Randomization-Study Session 1 | Adverse Event prior to intervention | 0 | 1 |
| Period 1: Randomization-Study Session 1 | Disliked mobile system | 0 | 1 |
| Period 1: Randomization-Study Session 1 | Regimen not compatible with study | 2 | 1 |
| Period 1: Randomization-Study Session 1 | Work or scheduling conflict | 2 | 3 |
| Period 2 | Disliked Mobile System | 2 | 0 |
| Period 2 | Work/Scheduling Conflict | 1 | 0 |
| Period 3 | Work/Scheduling Conflict | 0 | 1 |
Baseline characteristics
| Characteristic | Group A | Group B | Total |
|---|---|---|---|
| Age, Continuous | 42.7 years STANDARD_DEVIATION 13.5 | 41.9 years STANDARD_DEVIATION 10.1 | 42.3 years STANDARD_DEVIATION 11.9 |
| Hemoglobin A1c | 7.6 percent STANDARD_DEVIATION 1.08 | 7.24 percent STANDARD_DEVIATION 0.97 | 7.42 percent STANDARD_DEVIATION 1.03 |
| Race/Ethnicity, Customized Asian | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Caucasian/More than One Race | 38 Participants | 40 Participants | 78 Participants |
| Region of Enrollment United States | 40 participants | 40 participants | 80 participants |
| Sex: Female, Male Female | 27 Participants | 26 Participants | 53 Participants |
| Sex: Female, Male Male | 13 Participants | 14 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 93 | 0 / 93 | 0 / 93 | 0 / 93 |
| other Total, other adverse events | 5 / 93 | 14 / 93 | 7 / 93 | 9 / 93 |
| serious Total, serious adverse events | 1 / 93 | 1 / 93 | 0 / 93 | 1 / 93 |
Outcome results
Primary
Hemoglobin A1c
Overnight CLC achieved by USS+SAP(d) (also known as Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c \< 7.5% vs ≥7.5% and time of day.
Time frame: 8 weeks
Population: This primary analysis was confined to the phase of the study comparing SAP to Evening-Night CLC only when combining group A and B and included the baseline HbA1c and final HbA1c. Data on HbA1c by study phase is included in secondary outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A and Group B Combined | Hemoglobin A1c | HbA1c at baseline | 7.42 percentage of glycated hemoglobin | Standard Deviation 1.03 |
| Group A and Group B Combined | Hemoglobin A1c | HbA1c at end of study | 7.11 percentage of glycated hemoglobin | Standard Deviation 0.86 |
Primary
Time <70 mg/dl by CGM
Overnight CLC achieved by USS+SAP(d) (also known at Evening-Night CLC) will be superior to SAP alone in terms of reduced incidence and risk for hypoglycemia overnight without deterioration in hemoglobin A1c. Outcomes will be stratified by Hemoglobin A1c \< 7.5% vs ≥7.5% and time of day.
Time frame: 8 weeks
Population: This primary analysis was confined to the phase of the study comparing SAP to Evening-Night CLC only when combining group A and B. Data on 24/7 CLC phase is included in secondary outcomes.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A and Group B Combined | Time <70 mg/dl by CGM | CGM Time<70 mg/dL in Evening-Overnight CLC | 2.2 percentage of time | Standard Deviation 1.8 |
| Group A and Group B Combined | Time <70 mg/dl by CGM | CGM Time<70 mg/dL in SAP | 4.0 percentage of time | Standard Deviation 3.3 |
Comparison: The null hypothesis is that there is no difference in percentage of time \<70 mg/dL in SAP vs. evening-overnight CLC session. Change in HbA1c during study sessions was used as a covariate of the model.p-value: <0.000195% CI: [1.2, 2.4]Mixed Models Analysis
Secondary
CGM <70mg/dL
Percentage time \<70mg/dL measured by CGM in three study phases combining Group A and B.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | CGM <70mg/dL | 4.0 Percentage of time | Standard Deviation 3.3 |
| Evening and Overnight Closed-Loop Control | CGM <70mg/dL | 2.3 Percentage of time | Standard Deviation 1.7 |
| 24/7 Closed-Loop Control | CGM <70mg/dL | 1.8 Percentage of time | Standard Deviation 1.4 |
Secondary
Hemoglobin A1c by Study Session
Hemoglobin A1c after each 8 weeks study session by Group A and Group B.
Time frame: 8 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Group A and Group B Combined | Hemoglobin A1c by Study Session | Session 1 (Group A SAP; Group B evening-night CLC) | 7.3 percentage of glycated hemoglobin | Standard Deviation 0.83 |
| Group A and Group B Combined | Hemoglobin A1c by Study Session | Session 2 (Gp A Evening-NIght CLC;Gp B 24/7 CLC) | 7.12 percentage of glycated hemoglobin | Standard Deviation 0.79 |
| Group A and Group B Combined | Hemoglobin A1c by Study Session | Session 3 (Gp A 24/7 CLC; Gp B evening-night CLC | 7.13 percentage of glycated hemoglobin | Standard Deviation 0.8 |
| Group A and Group B Combined | Hemoglobin A1c by Study Session | Session 4 (Gp A Evening-Night CLC; Gp B SAP) | 7.1 percentage of glycated hemoglobin | Standard Deviation 0.73 |
| Evening and Overnight Closed-Loop Control | Hemoglobin A1c by Study Session | Session 4 (Gp A Evening-Night CLC; Gp B SAP) | 7.12 percentage of glycated hemoglobin | Standard Deviation 0.97 |
| Evening and Overnight Closed-Loop Control | Hemoglobin A1c by Study Session | Session 1 (Group A SAP; Group B evening-night CLC) | 7.01 percentage of glycated hemoglobin | Standard Deviation 0.76 |
| Evening and Overnight Closed-Loop Control | Hemoglobin A1c by Study Session | Session 3 (Gp A 24/7 CLC; Gp B evening-night CLC | 7.06 percentage of glycated hemoglobin | Standard Deviation 0.95 |
| Evening and Overnight Closed-Loop Control | Hemoglobin A1c by Study Session | Session 2 (Gp A Evening-NIght CLC;Gp B 24/7 CLC) | 6.95 percentage of glycated hemoglobin | Standard Deviation 0.68 |
Secondary
High Blood Glucose Index (HBGI)
Index measure of high blood glucose risk.
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | High Blood Glucose Index (HBGI) | 8.82 index | Standard Deviation 4.61 |
| Evening and Overnight Closed-Loop Control | High Blood Glucose Index (HBGI) | 6.97 index | Standard Deviation 3.52 |
| 24/7 Closed-Loop Control | High Blood Glucose Index (HBGI) | 6.53 index | Standard Deviation 2.86 |
Secondary
Low Blood Glucose Index (LBGI)
Index measure of low blood glucose risk. This is an index that indicates risk of hypoglycemia with low values indicating lower risk of hypoglycemia (particularly values 1 or lower).
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | Low Blood Glucose Index (LBGI) | 1.04 index | Standard Deviation 0.79 |
| Evening and Overnight Closed-Loop Control | Low Blood Glucose Index (LBGI) | 0.66 index | Standard Deviation 0.42 |
| 24/7 Closed-Loop Control | Low Blood Glucose Index (LBGI) | 0.57 index | Standard Deviation 0.34 |
Secondary
Mean Glucose by CGM
Mean glucose measured by CGM overall in mmol/L
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | Mean Glucose by CGM | 9.3 mmol/L | Standard Deviation 1.58 |
| Evening and Overnight Closed-Loop Control | Mean Glucose by CGM | 8.82 mmol/L | Standard Deviation 1.22 |
| 24/7 Closed-Loop Control | Mean Glucose by CGM | 8.74 mmol/L | Standard Deviation 0.99 |
Secondary
Time >180 mg/dL by CGM
Time in hyperglycemia range \>180 mg/dL measured by CGM
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | Time >180 mg/dL by CGM | 37.4 percentage of time | Standard Deviation 16.5 |
| Evening and Overnight Closed-Loop Control | Time >180 mg/dL by CGM | 30.1 percentage of time | Standard Deviation 13.7 |
| 24/7 Closed-Loop Control | Time >180 mg/dL by CGM | 28.7 percentage of time | Standard Deviation 11.4 |
Secondary
Time Between 70-180 mg/dL by CGM
Time in target range 70-180 mg/dL measured by CGM
Time frame: 8 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group A and Group B Combined | Time Between 70-180 mg/dL by CGM | 58.6 percentage of time | Standard Deviation 14.6 |
| Evening and Overnight Closed-Loop Control | Time Between 70-180 mg/dL by CGM | 67.6 percentage of time | Standard Deviation 12.9 |
| 24/7 Closed-Loop Control | Time Between 70-180 mg/dL by CGM | 69.5 percentage of time | Standard Deviation 10.9 |