Type 1 Diabetes
Conditions
Keywords
Advanced Hybrid Closed Loop, Multiple Daily Injections, Flash Glucose Monitoring, Continuous Glucose Monitoring
Brief summary
The purpose of this study evaluate the safety and efficacy of the Advanced Hybrid Closed Loop (AHCL) system in sub-optimally controlled patients with T1D, in comparison with Multiple Daily Injection (MDI) therapy with Flash Glucose Monitoring (FGM) or Continuous Glucose Monitoring (CGM). Patient with a diagnosis of Type 1 diabetes currently under MDI+ FGM or MDI+ CGM therapy will be enrolled.
Detailed description
This study is a pre-market, multi-center, prospective, open label, adaptative, randomized controlled trial in insulin-requiring adult subjects with type 1 diabetes on MDI therapy. The study will have three period: 1. Run-in Phase: The Run-in period is of 4 weeks (and can be extended for 2 additional ones) during which time a blinded CGM sensor will be worn for two weeks. 2. Study Phase: There will be a 6 months randomized study period with two arms: Treatment Arm (AHCL) and the Control Arm. 3. Continuation Phase: There will be a 6 months continuation phase during which time all the subjects will use the AHCL system. Approximately 124 subjects will be enrolled in the study up to 20 investigational centers in EMEA.
Interventions
OTHERMDI
Subject continues their standard Multiple Daily Injections therapy with FGM or RT-CGM
DEVICEAHCL
Subject starts using the Advance Hybrid Close Loop (AHCL) MiniMed™ 670G system version 4.0. Starting time depends on which Arm the subject is assigned to: if the subject is assigned to the Treatment Arm, then the intervention starts after the RUN-IN period. If the subject is assigned to the Control Arm the intervention will start after 6 months from the date of the enrollment.
Sponsors
Medtronic Diabetes
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
There will be 2 Cohort for this study: 1. Cohort A: Subjects on MDI + FGM will be randomized into: Treatment Arm (AHCL) and Control Arm (MDI+ FGM) 2. Cohort B: Subjects on MDI + Real-Time CGM will be randomized into: Treatment Arm (AHCL) and Control Arm (MDI+ CGM) (exploratory analysis)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Subject is age ≥ 18 years old at time of screening 2. Subject has a clinical diagnosis of Type 1 diabetes for ≥ 2 years prior to screening as determined via source documentation 3. On MDI therapy (defined as ≥ 3 insulin injections per day and/or a basal/bolus regimen) ≥ 2 years prior to screening 4. Subject has been followed and treated by the investigator at this investigational site for at least 3 months prior to screening and subject has already undergone local educational therapeutic programs. 5. Subject is using: * Flash Glucose Monitoring (FGM) for ≥ 3 months with a daily average number of scans ≥ 5 over and with sensor readings \> 70% of time over the previous month prior to screening (based on sensor usage from the download summary report of the FGM system over 30 days prior to screening) Or * Continuous Glucose Monitoring (CGM) for ≥ 3 months with a frequency of sensor use ≥ 70% of the time over the previous month prior to screening (based on download summary report from the CGM system over 30 days prior to screening). 6. Subject has a glycosylated hemoglobin (HbA1c) ≥ 8.0% (64 mmol/mol) at time of screening visit (as processed by a Central Lab). 7. Subject is willing to take or switch to one of the following insulins: 1. Humalog™ (insulin lispro injection) 2. NovoLog™ (insulin aspart) 8. Subject must have a minimum daily insulin requirement (Total Daily Dose) of ≥ 8 units and a maximum of 250 units. 9. Subject is willing to upload data from the study pump and meter, must have Internet access and a compatible computer system that meets the requirements for uploading the study pump data at home. 10. Subject is willing and able to sign and date informed consent, comply with all study procedures and wear all study devices, as required during the study.
Exclusion criteria
1. Subject has untreated Addison's disease, thyroid disorder, growth hormone deficiency, hypopituitarism or definite gastroparesis, per investigator judgment. 2. Subject is using pramlintide, DPP-4 inhibitor, GLP-1 agonists/mimetics, metformin, SGLT2 inhibitors at time of screening. 3. Subject has had renal failure defined by creatinine clearance \<30 ml/min, as assessed by local lab test ≤ 12 months before screening or performed at screening at local lab, as defined by the creatinine-based Cockcroft or MDRD equations. 4. Subject is planning to switch from FGM to CGM therapy during the 6 months study phase. Note: Subject randomized to Control Arm should remain on their current FGM or CGM therapy during the study phase and will be switched to AHCL during the continuation phase. 5. Subject has a history of hearing or vision impairment hindering perception of glucose display and alarms, or otherwise incapable of using the study devices, per investigator judgment. 6. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study. 7. Females who are sexually active and able to conceive will be excluded if they are not using an effective method of contraception and do not agree to continue using an effective method of contraception for the duration of the study, per investigator judgment. 8. Subject has any unresolved adverse skin conditions in the area of sensor placement (e.g. psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection). 9. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or device in the last 2 weeks before enrollment into this study, as per investigator judgment. 10. Subject is currently abusing illicit drugs, marijuana, alcohol or prescription drugs (other than nicotine), per investigator judgment. 11. Subject has any other disease or condition that may preclude the patient from participating in the study, per investigator judgment. 12. Subject is legally incompetent, illiterate or vulnerable person. 13. Research staff involved with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| HbA1c 6 Months Change Between AHCL and MDI | Baseline and end of 6-month study phase | The difference in the mean HbA1c change (6 months - baseline) between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| TIR Between 70-180 mg/dL | 6 months study phase | % Time spent within range with sensor glucose (SG) between 70 - 180 mg/dL (3.9-10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). |
| Time in Hyperglycemic Range | 6 months study phase | % Time spent in hyperglycemic range with SG \> 180 mg/dL (\> 10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A). |
| Hypoglycemic Events | 6 months study phase | Number of biochemical hypoglycemic events\< 54 mg/dL (3.0 mmol/L) (defined as sensor values \< 54 mg/dL (3.0 mmol/L) per 15 consecutive minutes (Danne, 2017). When the time between two successive events is less than 30 minutes, they will be combined and counted as one event. The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A) |
Other
| Measure | Time frame | Description |
|---|---|---|
| HbA1c 6 Months Change Within Group | End of 6-month study phase and end of 6-month continuation phase | The change in the mean HbA1c from end of 6-month study phase to end of 6-month continuation phase will be evaluated (Cohort A) |
| HbA1c 6 Months Change Between AHCL and MDI | Baseline and end of 6-month study phase | The difference in the mean HbA1c change (6 months - baseline) between the AHCL and the MDI + CGM arm will be evaluated (Cohort B). |
| HbA1c 12 Months Change Between Groups | Baseline through the end of 6-month continuation phase (a total of 12 months) | The difference in the mean HbA1c change (12 months - baseline) between treatment arm and control arm will be evaluated (Cohort A) |
| TIR Between 70-180 mg/dL | 6 months study phase | % Time spent within range with sensor glucose (SG) between 70 - 180 mg/dL (3.9-10.0 mmol/L). The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B). |
| Time in Hyperglycemic Range | 6 months study phase | % Time spent in hyperglycemic range with SG \> 180 mg/dL (\> 10.0 mmol/L). The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B). |
| Hypoglycemic Events | 6 months study phase | Number of biochemical hypoglycemic events\< 54 mg/dL (3.0 mmol/L) (defined as sensor values \< 54 mg/dL (3.0 mmol/L) per 15 consecutive minutes (Danne, 2017). When the time between two successive events is less than 30 minutes, they will be combined and counted as one event. The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B). |
Countries
France, Germany, United Kingdom
Participant flow
Recruitment details
Date of first subject enrollment: 13-JUL-2020, Date of last subject visit (of study phase): 02-DEC-2021 Date of last subject visit (of continuation phase): 30-MAY-2022
Pre-assignment details
122 adults with type 1 diabetes consented to participate in the study. Of them, 19 subjects are Screen Failure. After 8 patients early exited before randomization, 95 (82 in Cohort A, 13 in Cohort B) subjects were randomized in study phase.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A - Treatment Arm In study phase, subjects on MDI with Flash Glucose Monitoring (FGM) in run-in phase started using AHCL (stop MDI + FGM therapy at Visit 6A).
In continuation phase, subjects continued using AHCL. | 41 |
| Cohort A - Control Arm In study phase, subjects on MDI with Flash Glucose Monitoring (FGM) in run-in phase continued using MDI + FGM.
In continuation phase, subjects started using AHCL. | 41 |
| Cohort B - Treatment Arm In study phase, subjects on MDI + Real-Time CGM in run-in phase started using AHCL (stop MDI + CGM therapy at Visit 6A).
In continuation phase, subjects continued using AHCL. | 8 |
| Cohort B - Control Arm In study phase, subjects on MDI + Real-Time CGM in run-in phase continued using MDI + CGM.
In continuation phase, subjects started using AHCL. | 5 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Continuation Phase | Adverse Event | 0 | 1 | 0 | 0 |
| Continuation Phase | Physician Decision | 1 | 2 | 1 | 0 |
| Continuation Phase | Withdrawal by Subject | 0 | 4 | 0 | 0 |
| Study Phase | Withdrawal by Subject | 5 | 2 | 0 | 0 |
Baseline characteristics
| Characteristic | Cohort A - Treatment Arm | Cohort A - Control Arm | Cohort B - Treatment Arm | Cohort B - Control Arm | Total |
|---|---|---|---|---|---|
| Age, Continuous | 41.5 Years STANDARD_DEVIATION 11.63 | 39.7 Years STANDARD_DEVIATION 13.12 | 45.4 Years STANDARD_DEVIATION 13.32 | 36.2 Years STANDARD_DEVIATION 15.8 | 40.7 Years STANDARD_DEVIATION 12.58 |
| HbA1c | 9.00 Percentage STANDARD_DEVIATION 0.972 | 9.07 Percentage STANDARD_DEVIATION 0.716 | 8.90 Percentage STANDARD_DEVIATION 0.457 | 9.46 Percentage STANDARD_DEVIATION 0.611 | 9.05 Percentage STANDARD_DEVIATION 0.815 |
| Race and Ethnicity Not Collected | — | — | — | — | 0 Participants |
| Sex: Female, Male Female | 22 Participants | 16 Participants | 3 Participants | 3 Participants | 44 Participants |
| Sex: Female, Male Male | 19 Participants | 25 Participants | 5 Participants | 2 Participants | 51 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 17 | 0 / 41 | 0 / 41 | 0 / 8 | 0 / 5 | 0 / 88 |
| other Total, other adverse events | 21 / 105 | 1 / 17 | 19 / 41 | 18 / 41 | 2 / 8 | 0 / 5 | 31 / 88 |
| serious Total, serious adverse events | 1 / 105 | 1 / 17 | 1 / 41 | 1 / 41 | 1 / 8 | 0 / 5 | 2 / 88 |
Outcome results
Primary
HbA1c 6 Months Change Between AHCL and MDI
The difference in the mean HbA1c change (6 months - baseline) between the AHCL and the MDI + FGM arm will be evaluated (Cohort A).
Time frame: Baseline and end of 6-month study phase
Population: Study phase: 82 subjects in Cohort A. 74 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Between AHCL and MDI | -1.54 Percentage of HbA1c | Standard Error 0.729 |
| Cohort A - Control Arm | HbA1c 6 Months Change Between AHCL and MDI | -0.20 Percentage of HbA1c | Standard Error 0.797 |
p-value: <0.000195% CI: [-1.74, -1.1]linear mixed model
Secondary
Hypoglycemic Events
Number of biochemical hypoglycemic events\< 54 mg/dL (3.0 mmol/L) (defined as sensor values \< 54 mg/dL (3.0 mmol/L) per 15 consecutive minutes (Danne, 2017). When the time between two successive events is less than 30 minutes, they will be combined and counted as one event. The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A)
Time frame: 6 months study phase
Population: Study phase: 82 subjects in Cohort A. 67 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | Hypoglycemic Events | 1.29 Events per week | Standard Error 1.322 |
| Cohort A - Control Arm | Hypoglycemic Events | 0.98 Events per week | Standard Error 1.436 |
p-value: 0.622795% CI: [-0.37, 0.61]linear mixed model
Secondary
Time in Hyperglycemic Range
% Time spent in hyperglycemic range with SG \> 180 mg/dL (\> 10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A).
Time frame: 6 months study phase
Population: Study phase: 82 subjects in Cohort A. 67 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | Time in Hyperglycemic Range | 26.74 Percentage of Time | Standard Error 10.444 |
| Cohort A - Control Arm | Time in Hyperglycemic Range | 53.81 Percentage of Time | Standard Error 16.465 |
p-value: <0.000195% CI: [-34.16, -21.55]linear mixed model
Secondary
TIR Between 70-180 mg/dL
% Time spent within range with sensor glucose (SG) between 70 - 180 mg/dL (3.9-10.0 mmol/L). The difference in the mean between the AHCL and the MDI + FGM arm will be evaluated (Cohort A).
Time frame: 6 months study phase
Population: Study phase: 82 subjects in Cohort A. 67 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | TIR Between 70-180 mg/dL | 70.63 Percentage of Time | Standard Error 9.7 |
| Cohort A - Control Arm | TIR Between 70-180 mg/dL | 43.59 Percentage of Time | Standard Error 15.369 |
p-value: <0.000195% CI: [21.59, 33.6]linear mixed model
Other Pre-specified
HbA1c 12 Months Change Between Groups
The difference in the mean HbA1c change (12 months - baseline) between treatment arm and control arm will be evaluated (Cohort B).
Time frame: Baseline through the end of 6-month continuation phase (a total of 12 months).
Population: Overall study: 13 subjects in Cohort B. 9 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 12 Months Change Between Groups | -1.33 Percentage of HbA1c | Standard Error 1.122 |
| Cohort A - Control Arm | HbA1c 12 Months Change Between Groups | -1.30 Percentage of HbA1c | Standard Error 0.529 |
Other Pre-specified
HbA1c 12 Months Change Between Groups
The difference in the mean HbA1c change (12 months - baseline) between treatment arm and control arm will be evaluated (Cohort A)
Time frame: Baseline through the end of 6-month continuation phase (a total of 12 months)
Population: Overall study: 82 subjects in Cohort A. 66 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 12 Months Change Between Groups | -1.47 Percentage of HbA1c | Standard Error 0.829 |
| Cohort A - Control Arm | HbA1c 12 Months Change Between Groups | -1.58 Percentage of HbA1c | Standard Error 0.828 |
Other Pre-specified
HbA1c 6 Months Change Between AHCL and MDI
The difference in the mean HbA1c change (6 months - baseline) between the AHCL and the MDI + CGM arm will be evaluated (Cohort B).
Time frame: Baseline and end of 6-month study phase
Population: Study phase: 13 subjects in Cohort B. 12 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Between AHCL and MDI | -1.70 Percentage of HbA1c | Standard Error 1.039 |
| Cohort A - Control Arm | HbA1c 6 Months Change Between AHCL and MDI | -0.60 Percentage of HbA1c | Standard Error 1.259 |
95% CI: [-2.17, 0]linear mixed model
Other Pre-specified
HbA1c 6 Months Change Within Group
The change in the mean HbA1c from end of 6-month study phase to end of 6-month continuation phase will be evaluated (Cohort B).
Time frame: End of 6-month study phase and end of 6-month continuation phase
Population: Continuation phase: 5 subjects in Cohort B Control Arm. 3 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Within Group | -0.67 Percentage of HbA1c | Standard Error 0.551 |
Other Pre-specified
HbA1c 6 Months Change Within Group
The change in the mean HbA1c from end of 6-month study phase to end of 6-month continuation phase will be evaluated (Cohort A)
Time frame: End of 6-month study phase and end of 6-month continuation phase
Population: Continuation phase: 36 subjects in Cohort A Treatment Arm. 33 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Within Group | 0.16 Percentage of HbA1c | Standard Error 0.491 |
Other Pre-specified
HbA1c 6 Months Change Within Group
The change in the mean HbA1c from end of 6-month study phase to end of 6-month continuation phase will be evaluated (Cohort A)
Time frame: End of 6-month study phase and end of 6-month continuation phase
Population: Continuation phase: 38 subjects in Cohort A Control Arm. 31 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Within Group | -1.36 Percentage of HbA1c | Standard Error 0.777 |
Other Pre-specified
HbA1c 6 Months Change Within Group
The change in the mean HbA1c from end of 6-month study phase to end of 6-month continuation phase will be evaluated (Cohort B).
Time frame: End of 6-month study phase and end of 6-month continuation phase
Population: Continuation phase: 8 subjects in Cohort B Treatment Arm. 5 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | HbA1c 6 Months Change Within Group | 0.02 Percentage of HbA1c | Standard Error 0.466 |
Other Pre-specified
Hypoglycemic Events
Number of biochemical hypoglycemic events\< 54 mg/dL (3.0 mmol/L) (defined as sensor values \< 54 mg/dL (3.0 mmol/L) per 15 consecutive minutes (Danne, 2017). When the time between two successive events is less than 30 minutes, they will be combined and counted as one event. The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B).
Time frame: 6 months study phase
Population: Study phase: 13 subjects in Cohort B. 13 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | Hypoglycemic Events | 1.07 Events per week | Standard Error 1.327 |
| Cohort A - Control Arm | Hypoglycemic Events | 0.93 Events per week | Standard Error 1.135 |
95% CI: [-1.32, 0.59]linear mixed model
Other Pre-specified
Time in Hyperglycemic Range
% Time spent in hyperglycemic range with SG \> 180 mg/dL (\> 10.0 mmol/L). The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B).
Time frame: 6 months study phase
Population: Study phase: 13 subjects in Cohort B. 13 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | Time in Hyperglycemic Range | 23.97 Percentage of Time | Standard Error 13.512 |
| Cohort A - Control Arm | Time in Hyperglycemic Range | 50.88 Percentage of Time | Standard Error 15.63 |
95% CI: [-45.27, -11.64]linear mixed model
Other Pre-specified
TIR Between 70-180 mg/dL
% Time spent within range with sensor glucose (SG) between 70 - 180 mg/dL (3.9-10.0 mmol/L). The difference in the mean between the AHCL and the MDI + CGM arm will be evaluated (Cohort B).
Time frame: 6 months study phase
Population: Study phase: 13 subjects in Cohort B. 13 subjects have available measurements.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cohort A - Treatment Arm | TIR Between 70-180 mg/dL | 73.63 Percentage of Time | Standard Error 13.749 |
| Cohort A - Control Arm | TIR Between 70-180 mg/dL | 46.41 Percentage of Time | Standard Error 12.547 |
95% CI: [12.34, 45.28]linear mixed model