Type 1 Diabetes Mellitus
Conditions
Brief summary
This study is a Safety Evaluation of the Advanced Hybrid Closed Loop (AHCL) System in Type 1 Adult and Pediatric Subjects.
Detailed description
The purpose of this study is to evaluate the safety of the Advanced Hybrid Closed Loop system (AHCL) in type 1 diabetes adult and pediatric subjects in a home setting. The main objective in conducting this research is to collect data from patients who use the AHCL system at home, at work, at school and everywhere else. Subjects will use 670G 4.0 system with Guardian Sensor 3 (GS3) during study period, and will be allowed to participate in continued access phase, and use 670G 4.0 system with GS3 and 780G system with Guardian 4 Sensor (G4S).
Interventions
DEVICEAHCL insulin pump system
670G 4.0 system with GS3; 780G system with G4S (continued access phase);
Sponsors
Medtronic Diabetes
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Subject is age 7-75 years at time of Screening 2. Subjects 14-75 years of age: A clinical diagnosis of type 1 diabetes for 2 years or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis 3. Subjects 7-13 years of age: A clinical diagnosis of type 1 diabetes for 1 year or more as determined via medical record or source documentation by an individual qualified to make a medical diagnosis Study-specific inclusion criteria 4. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily 5. Subject is willing to perform required sensor calibrations 6. Subject is willing to wear the system continuously throughout the study 7. Subject must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units 8. Subject has a Glycosylated hemoglobin (HbA1c) less than 10% (as processed by Central Lab) at time of Screening visit Note: All HbA1c blood specimens will be sent to and tested by a NGSP certified Central Laboratory. HbA1c testing must follow National Glycohemoglobin Standardization Program (NGSP) standards. 9. Subject has TSH in the normal range OR if the TSH is out of normal reference range the Free T3 is below or within the lab's reference range and Free T4 is within the normal reference range. 10. Pump therapy for greater than 6 months prior to screening (with or without CGM experience) 11. Subject must have a companion or caregiver available at night for the duration of the study period who resides (or will live) in in the same building (or home). A companion or caregiver should also be available during exercise challenges in the same building, home or location (if not at home). This requirement may be verified by subject report at screening visit. 12. Subject willing to upload data from the study pump, must have Internet access and a computer system that meets the requirements for uploading the study pump 13. If subject has celiac disease, it has been adequately treated as determined by the investigator 14. Subject is willing to take one of the following insulins and can financially support the use of either of the 2 insulin preparations throughout the course of the study (i.e. co-payments for insulin with insurance or able to pay full amount) * Humalog™\* (insulin lispro injection) * NovoLog™\* (insulin aspart) 15. Subjects with history of cardiovascular event 1 year or more from the time of screening must have an EKG within 6 months prior to screening or during screening. If subject has an abnormal EKG, participation is allowed if there is clearance from a cardiologist 16. Subjects with the 3 or more cardiovascular risk factors listed below must have an EKG within 6 months prior to screening or during screening. If subject has an abnormal EKG, participation is allowed if there is clearance from a cardiologist a. Cardiovascular risk factors include: * Age \>35 years * Type 1 diabetes of \>15 years' duration * Presence of any additional risk factor for coronary artery disease * Presence of microvascular disease (proliferative retinopathy or nephropathy, including microalbuminuria) * Presence of peripheral vascular disease * Presence of autonomic neuropathy 17. Subjects with history of cardiovascular event 1 year or more from the time of screening must have a stress test within 6 months prior to screening or during run in period. If subject fails stress test, participation is allowed if there is clearance from a cardiologist
Exclusion criteria
1. Subject has a history of 1 or more episodes of severe hypoglycemia, which resulted in any the following during the 6 months prior to Screening: 1. Medical assistance (i.e. Paramedics, Emergency Room (ER) or Hospitalization) 2. Coma 3. Seizures 2. Subject has been hospitalized or has visited the ER in the 6 months prior to Screening resulting in a primary diagnosis of uncontrolled diabetes 3. Subject has had Diabetic Ketoacidosis (DKA) in the 6 months prior to Screening. 4. Subject has Hypoglycemia Unawareness, as measured by the Gold questionnaire (Gold, MacLeod et al. 1994) at Screening 5. Subject is unable to tolerate tape adhesive in the area of sensor placement 6. Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, dermatitis herpetiformis, rash, Staphylococcus infection) 7. Women of child-bearing potential who have a positive pregnancy test at Screening or plan to become pregnant during the course of the study 8. 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 as determined by investigator. 9. Subject has had any of the following cardiovascular events within 1 year of screening: myocardial infarction, unstable angina, coronary artery bypass surgery, coronary artery stenting, transient ischemic attack, cerebrovascular accident, angina, congestive heart failure, ventricular rhythm disturbances or thromboembolic disease 10. Subject is being treated for hyperthyroidism at time of Screening 11. Subject has a diagnosis of adrenal insufficiency 12. Subject has taken any oral, injectable, or intravenous (IV) glucocorticoids within 8 weeks from time of Screening, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study 13. Subject is actively participating in an investigational study (drug or device) wherein he/she has received treatment from an investigational study drug or investigational study device in the last 2 weeks 14. Subject is currently abusing illicit drugs 15. Subject is currently abusing marijuana 16. Subject is currently abusing prescription drugs 17. Subject is currently abusing alcohol 18. Subject is using pramlintide (Symlin), DPP-4 inhibitor, liraglutide (Victoza or other GLP-1 agonists), metformin, canagliflozin (Invokana or other SGLT2 inhibitors) at time of Screening 19. Subject has a history of visual impairment which would not allow subject to participate in the study and perform all study procedures safely, as determined by the investigator 20. Subject has elective surgery planned that requires general anesthesia during the course of the study 21. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of Screening 22. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation 23. Subject diagnosed with current eating disorder such as anorexia or bulimia 24. Subject has been diagnosed with chronic kidney disease that results in chronic anemia 25. Subject has a hematocrit that is below the normal reference range of lab used. 26. Subject is on dialysis 27. Subject has serum creatinine of \>2 mg/dL. 28. Research staff involved with the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in HbA1c | Baseline to End of 3-Month Study Period | The overall mean difference of the change in HbA1c from baseline to end of 3-month Study Period. |
| Change in Percentage of Euglycemia | Baseline to End of 3-Month Study Period | The overall mean change in % of time in euglycemia (70-180 mg/dL) from baseline to end of 3-month Study Period will be estimated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Severe Hypoglycemic Event | 3-month Study Period | Number of severe hypoglycemic events occurred during 3-month Study Period |
| Number of Diabetic Ketoacidosis (DKA) Event | 3-month Study Period | Number of Diabetic Ketoacidosis (DKA) event occurred during 3-month Study Period |
| Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | Baseline to End of 3-Month Study Period | The overall mean change in % of time in hypoglycemic range (\<70 mg/dL) from baseline to end of 3-month Study Period will be estimated. |
Countries
United States
Participant flow
Pre-assignment details
329 subjects (179 with age 7-17 and 150 with age 18-75) enrolled at the beginning, with 25 (10 with age 7-17 and 15 with age 18-75) screen failure, 15 subjects (8 with age 7-17 and 7 with age 18-75) early withdrawn, and 1 subject (age 7-17) who never used AHCL, 288 subjects (160 with age 7-17 and 128 with age 18-75) were left as the Intention to Treat Population and started the study. After completing the study, 207 (130 with age 7-17 and 77 with age 18-75) entered the Continued Access Period
Participants by arm
| Arm | Count |
|---|---|
| Subjects 7-17 Years of Age Subjects 7-17 years of age wearing Advanced Hybrid Closed Loop pump system and using AHCL during Study Period | 160 |
| Subjects 18-75 Years of Age Subjects 18-75 years of age wearing Advanced Hybrid Closed Loop pump system and using AHCL during Study Period | 128 |
| Total | 288 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Withdrawal by Parent/Guardian | 6 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 3 |
Baseline characteristics
| Characteristic | Subjects 7-17 Years of Age | Subjects 18-75 Years of Age | Total |
|---|---|---|---|
| Age, Continuous | 11.3 years STANDARD_DEVIATION 2.5 | 43.5 years STANDARD_DEVIATION 15.2 | 25.6 years STANDARD_DEVIATION 19.1 |
| BMI | 19.7 kg/m^2 STANDARD_DEVIATION 3.5 | 28.4 kg/m^2 STANDARD_DEVIATION 5.6 | 23.6 kg/m^2 STANDARD_DEVIATION 6.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 7 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 148 Participants | 120 Participants | 268 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 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 | 1 Participants | 5 Participants |
| Race (NIH/OMB) More than one race | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) White | 144 Participants | 123 Participants | 267 Participants |
| Sex: Female, Male Female | 83 Participants | 69 Participants | 152 Participants |
| Sex: Female, Male Male | 77 Participants | 59 Participants | 136 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 / 160 | 0 / 128 | 0 / 130 | 0 / 77 |
| other Total, other adverse events | 72 / 160 | 44 / 128 | 99 / 130 | 64 / 77 |
| serious Total, serious adverse events | 1 / 160 | 3 / 128 | 3 / 130 | 8 / 77 |
Outcome results
Primary
Change in HbA1c
The overall mean difference of the change in HbA1c from baseline to end of 3-month Study Period.
Time frame: Baseline to End of 3-Month Study Period
Population: Intention to Treat Population with available data. Twenty-four subjects aged 7-17 and one subject aged 18-75 did not collect A1C at the end of the study period, so 136 subjects aged 7-17 and 127 subjects aged 18-75 were analyzed at end of study period and the change from baseline to end of study period.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects 7-17 Years of Age | Change in HbA1c | End of Study | 7.4 percentage | Standard Deviation 0.7 |
| Subjects 7-17 Years of Age | Change in HbA1c | Baseline | 7.9 percentage | Standard Deviation 0.9 |
| Subjects 7-17 Years of Age | Change in HbA1c | Change from Baseline to End of Study | -0.5 percentage | Standard Deviation 0.7 |
| Subjects 18-75 Years of Age | Change in HbA1c | Baseline | 7.4 percentage | Standard Deviation 0.8 |
| Subjects 18-75 Years of Age | Change in HbA1c | End of Study | 6.9 percentage | Standard Deviation 0.5 |
| Subjects 18-75 Years of Age | Change in HbA1c | Change from Baseline to End of Study | -0.5 percentage | Standard Deviation 0.6 |
Primary
Change in Percentage of Euglycemia
The overall mean change in % of time in euglycemia (70-180 mg/dL) from baseline to end of 3-month Study Period will be estimated.
Time frame: Baseline to End of 3-Month Study Period
Population: Intention to Treat Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects 7-17 Years of Age | Change in Percentage of Euglycemia | 3 Months Study Period | 70.3 percentage | Standard Deviation 6.5 |
| Subjects 7-17 Years of Age | Change in Percentage of Euglycemia | Baseline | 59.4 percentage | Standard Deviation 11.8 |
| Subjects 7-17 Years of Age | Change in Percentage of Euglycemia | Change from Baseline to 3 Months Study Period | 11.0 percentage | Standard Deviation 9.1 |
| Subjects 18-75 Years of Age | Change in Percentage of Euglycemia | 3 Months Study Period | 75.0 percentage | Standard Deviation 7.2 |
| Subjects 18-75 Years of Age | Change in Percentage of Euglycemia | Baseline | 70.5 percentage | Standard Deviation 9.8 |
| Subjects 18-75 Years of Age | Change in Percentage of Euglycemia | Change from Baseline to 3 Months Study Period | 4.6 percentage | Standard Deviation 5.9 |
Secondary
Change in Percent of Time in Hypoglycemic Range (<70 mg/dL)
The overall mean change in % of time in hypoglycemic range (\<70 mg/dL) from baseline to end of 3-month Study Period will be estimated.
Time frame: Baseline to End of 3-Month Study Period
Population: Intention to Treat Population
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Subjects 7-17 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | Baseline | 2.7 percentage | Standard Deviation 2 |
| Subjects 7-17 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | 3 Months Study Period | 2.7 percentage | Standard Deviation 1.6 |
| Subjects 7-17 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | Change from Baseline to 3 Months Study Period | -0.0 percentage | Standard Deviation 1.7 |
| Subjects 18-75 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | Baseline | 3.4 percentage | Standard Deviation 3 |
| Subjects 18-75 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | 3 Months Study Period | 2.3 percentage | Standard Deviation 1.7 |
| Subjects 18-75 Years of Age | Change in Percent of Time in Hypoglycemic Range (<70 mg/dL) | Change from Baseline to 3 Months Study Period | -1.0 percentage | Standard Deviation 2.2 |
Secondary
Number of Diabetic Ketoacidosis (DKA) Event
Number of Diabetic Ketoacidosis (DKA) event occurred during 3-month Study Period
Time frame: 3-month Study Period
Population: Intention to Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects 7-17 Years of Age | Number of Diabetic Ketoacidosis (DKA) Event | 0 Events |
| Subjects 18-75 Years of Age | Number of Diabetic Ketoacidosis (DKA) Event | 0 Events |
Secondary
Number of Severe Hypoglycemic Event
Number of severe hypoglycemic events occurred during 3-month Study Period
Time frame: 3-month Study Period
Population: Intention to Treat Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Subjects 7-17 Years of Age | Number of Severe Hypoglycemic Event | 0 Events |
| Subjects 18-75 Years of Age | Number of Severe Hypoglycemic Event | 0 Events |