Multi-center Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control at Home

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and effectiveness of the Hybrid Closed Loop system (HCL) in adult and pediatric patients with type 1 diabetes in the home setting. A diverse population of patients with type 1 diabetes will be studied. The study population will have a large range for duration of diabetes and glycemic control, as measured by glycosylated hemoglobin (A1C). They will be enrolled in the study regardless of their prior diabetes regimen, including using Multiple Daily Injections (MDI), Continuous Subcutaneous Insulin Infusion (CSII) or Sensor-Augmented Pump therapy (SAP)

Detailed Description
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This is a 6 month, multi-center, randomized, parallel, adaptive study in type 1 diabetes with a 6 month continuation period. The study will have three periods, per Cohort: Run-in Period: The run-in period can be up to 60 days during which time a blinded CGM sensor will be worn for two weeks. Study Period: There will be a 6 month randomized study period with two arms: The HCL system and Control. Continuation Period: There will be a 6 month continuation period during which time all subjects will use the HCL system with Auto Mode. Up to 1500 subjects will be enrolled in order to have 1000 subjects complete the study. Up to 70 investigational Centers in the US, Europe, Canada, Australia and New Zealand will be enrolled.

Official Title
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Multi-center, Randomized, Parallel, Adaptive, Controlled Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control (CSII, MDI and SAP) at Home

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: 670G and 770G Insulin Pump
* Device: Subject's Current Diabetes Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Subject is age 2-80 years at time of screening US, Canada, Australia and New Zealand: Subjects 2-80 years of age will be allowed to enroll in the post approval study. Europe: Only subjects ≥7 years of age are allowed to enroll in the post-market study. Subjects who are 2-21 years are determined by the investigator to have the appropriate, requisite support (family, caregiver or social network) to successfully participate in this study Subject must have a minimum daily insulin requirement (Total Daily Dose) of equal to or greater than 8 units/day Subjects who are determined by the investigator to be psychologically sound in order to successfully participate in this study Subject has been diagnosed with type 1 diabetes for at least three months Note: Determination of classification for diabetes will be based on American Diabetes Association Clinical Practice Guidelines accounting for several patient characteristics such as: age of onset, patient's weight or BMI, history of diabetic ketoacidosis, history of therapy management, if available in the medical records. Subject must be on one of the following management therapies: Multiple daily injections defined by use of rapid analogue with meals and approved long acting analogue (e.g. detemir or glargine) with or without CGM Insulin pump therapy with or without CGM Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily Subject is willing to perform required study procedures Subject is willing to wear the system continuously throughout the study for at least 80% of the time. Subject is willing to upload data at least weekly from the study pump/meter, must have Internet access and a computer system that meets the requirements for uploading the study pump/meter for data collection Subject must be willing to use the study glucose meter system (i.e. along with study meter strips). If subject has celiac disease, it has been adequately treated as determined by the investigator Subject with the diagnosis of 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, within 1 year of screening, will be included in the study with the consent of the Investigator Subject is willing to take one of the following insulins and can financially afford to use 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) Exclusion Criteria: Subject participated in any Closed Loop study in the past. Subject is unable to tolerate tape adhesive in the area of sensor placement Subject has any unresolved adverse skin condition in the area of sensor placement (e.g., psoriasis, rash, Staphylococcus infection) or area of infusion set placement Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study Subject is being treated for hyperthyroidism at time of screening Subject has an abnormality (out of reference range) in thyroid-stimulating hormone (TSH) at time of screening visit. TSH is not required for subjects 2-13 years of age. Subject has taken any oral, injectable, or IV glucocorticoids within 8 weeks from time of screening visit, or plans to take any oral, injectable, or IV glucocorticoids during the course of the study. 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 Subject is currently abusing illicit drugs or marijuana Subject is currently abusing prescription drugs Subject is currently abusing alcohol Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, biguanides, DPP-4 inhibitors or sulfonylureas at time of screening Subject is using hydroxyurea at the time of screening or plans to use it during the study 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 Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation Subject diagnosed with current moderate to severe eating disorder such as anorexia or bulimia Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting in chronic anemia Subjects who are currently being actively treated for cancer. Subject who is designated as a research staff member for this study

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: There will be three cohorts sequentially enrolled for the study. Cohort 1: Continuous Subcutaneous Insulin Infusion (CSII cohort): randomized to HCL (treatment arm) or CSII (Control arm) Cohort 2: Multiple Daily Injections (MDI cohort): randomized to HCL (treatment arm) or MDI (Control arm) Cohort 3: Sensor-Augmented Pump therapy (SAP cohort): randomized to HCL (treatment arm) or SAP (Control arm) Note: Subjects 2-6 years of age will automatically enter the HCL arm at the end of the run-in period
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hybrid Closed Loop Arm<br>The HCL Arm will use the MiniMed System (i.e., using Auto Mode) for 6 months during the study period. | Device: 670G and 770G Insulin Pump<br>* Medtronic 670G and 770G Hybrid Closed Loop Systems<br>|
| Active Comparator: Control Arm<br>The Control Arm will use individual subject's current diabetes therapy: CSII (Continuous Subcutaneous Insulin Infusion), MDI (Multiple Daily Injections) or SAP (Sensor Augmented Pump). Each cohort (CSII, MDI, or SAP) will be used as the control arm to be compared to the experimental arm (HCL). | Device: Subject's Current Diabetes Therapy<br>* Subject will use current diabetes therapy: CSII (Continuous Subcutaneous Insulin Infusion), MDI (Multiple Daily Injections) or SAP (Sensor Augmented Pump).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSII Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% | CSII Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c > 8% | 6 months | 
| CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% | CSII Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c ≤ 8% | 6 months | 
| MDI Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% | MDI Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c > 8% | 6 months | 
| MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% | MDI Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c ≤ 8% | 6 months | 
| SAP Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% | SAP Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c > 8% | 6 months | 
| SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% | SAP Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c ≤ 8% | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% | CSII Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c > 8% | 6 months | 
| CSII Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% | CSII Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c ≤ 8% | 6 months | 
| CSII Cohort: Time in Hypoglycemic Range during Night for all subjects | CSII Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects | 6 months | 
| CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | CSII Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | 6 months | 
| CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | CSII Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | 6 months | 
| CSII Cohort: Time in Hypoglycemic Range during Day and Night for all subjects | CSII Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects | 6 months | 
| CSII Cohort: Change in A1C for all subjects | CSII Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit for all subjects | 6 months | 
| MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% | MDI Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c > 8% | 6 months | 
| MDI Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% | MDI Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c ≤ 8% | 6 months | 
| MDI Cohort: Time in Hypoglycemic Range during Night for all subjects | MDI Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects | 6 months | 
| MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | MDI Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | 6 months | 
| MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | MDI Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | 6 months | 
| MDI Cohort: Time in Hypoglycemic Range during Day and Night for all subjects | MDI Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects | 6 months | 
| MDI Cohort: Change in A1C for all subjects | MDI Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit for all subjects | 6 months | 
| SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% | SAP Cohort: Time with sensor glucose (SG) below 70 mg/dL (3.9mmol/L) during the six-month study period. This is only for subjects with baseline A1c > 8% | 6 months | 
| SAP Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% | SAP Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit. This is only for subjects with baseline A1c ≤ 8% | 6 months | 
| SAP Cohort: Time in Hypoglycemic Range during Night for all subjects | SAP Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects | 6 months | 
| SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | SAP Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects | 6 months | 
| SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | SAP Cohort: Time in target range measures the time with SG in target range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects | 6 months | 
| SAP Cohort: Time in Hypoglycemic Range during Day and Night for all subjects | SAP Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects | 6 months | 
| SAP Cohort: Change in A1C for all subjects | SAP Cohort: Change in A1C from baseline to the end of the six-month treatment period, defined as A1C measured at the six-month treatment visit minus A1C measured at the randomization visit for all subjects | 6 months |