Clinical trial NCT02748018: Multi-center Trial in Adult and Pediatric Patients With Type 1 Diabetes Using Hybrid Closed Loop System and Control at Home
Official title: 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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Type 1 Diabetes
Lead sponsor: Medtronic Diabetes
Sponsor class: INDUSTRY
First posted: 2016-04-22
Enrollment: 280
Sex: ALL
Minimum age (years): 2
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

Brief summary: 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: 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:

1. 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.
2. Study Period: There will be a 6 month randomized study period with two arms: The HCL system and Control.
3. 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.

Eligibility criteria: Inclusion Criteria

1. Subject is age 2-80 years at time of screening

   1. US, Canada, Australia and New Zealand: Subjects 2-80 years of age will be allowed to enroll in the post approval study.
   2. Europe: Only subjects ≥7 years of age are allowed to enroll in the post-market study.
2. 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
3. Subject must have a minimum daily insulin requirement (Total Daily Dose) of equal to or greater than 8 units/day
4. Subjects who are determined by the investigator to be psychologically sound in order to successfully participate in this study
5. 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.
6. Subject must be on one of the following management therapies:

   1. 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
   2. Insulin pump therapy with or without CGM
7. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily
8. Subject is willing to perform required study procedures
9. Subject is willing to wear the system continuously throughout the study for at least 80% of the time.
10. 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
11. Subject must be willing to use the study glucose meter system (i.e. along with study meter strips).
12. If subject has celiac disease, it has been adequately treated as determined by the investigator
13. 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
14. 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)

    1. Humalog® (insulin lispro injection)
    2. NovoLog® (insulin aspart)

Exclusion Criteria:

1. Subject participated in any Closed Loop study in the past.
2. Subject is unable to tolerate tape adhesive in the area of sensor placement
3. 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
4. Women of child-bearing potential who have a positive pregnancy test at screening or plan to become pregnant during the course of the study
5. Subject is being treated for hyperthyroidism at time of screening
6. 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.
7. 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.
8. 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
9. Subject is currently abusing illicit drugs or marijuana
10. Subject is currently abusing prescription drugs
11. Subject is currently abusing alcohol
12. Subject is using pramlintide (Symlin), SGLT2 inhibitors, GLP agonists, biguanides, DPP-4 inhibitors or sulfonylureas at time of screening
13. Subject is using hydroxyurea at the time of screening or plans to use it during the study
14. 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
15. Subject has a sickle cell disease, hemoglobinopathy; or has received red blood cell transfusion or erythropoietin within 3 months prior to time of screening
16. Subject plans to receive red blood cell transfusion or erythropoietin over the course of study participation
17. Subject diagnosed with current moderate to severe eating disorder such as anorexia or bulimia
18. Subject has been diagnosed with chronic kidney disease requiring dialysis or resulting in chronic anemia
19. Subjects who are currently being actively treated for cancer.
20. Subject who is designated as a research staff member for this study

Primary outcomes:
measure: CSII Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
measure: MDI Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
measure: SAP Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
Secondary outcomes:
measure: CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: CSII Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
measure: CSII Cohort: Time in Hypoglycemic Range during Night for all subjects
timeFrame: 6 months
measure: CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects
timeFrame: 6 months
measure: CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects
timeFrame: 6 months
measure: CSII Cohort: Time in Hypoglycemic Range during Day and Night for all subjects
timeFrame: 6 months
measure: CSII Cohort: Change in A1C for all subjects
timeFrame: 6 months
measure: MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: MDI Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
measure: MDI Cohort: Time in Hypoglycemic Range during Night for all subjects
timeFrame: 6 months
measure: MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects
timeFrame: 6 months
measure: MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects
timeFrame: 6 months
measure: MDI Cohort: Time in Hypoglycemic Range during Day and Night for all subjects
timeFrame: 6 months
measure: MDI Cohort: Change in A1C for all subjects
timeFrame: 6 months
measure: SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8%
timeFrame: 6 months
measure: SAP Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8%
timeFrame: 6 months
measure: SAP Cohort: Time in Hypoglycemic Range during Night for all subjects
timeFrame: 6 months
measure: SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects
timeFrame: 6 months
measure: SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects
timeFrame: 6 months
measure: SAP Cohort: Time in Hypoglycemic Range during Day and Night for all subjects
timeFrame: 6 months
measure: SAP Cohort: Change in A1C for all subjects
timeFrame: 6 months
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: Scripps Health System
state: California
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Sacramento
country: United States
facility: Center of Excellence in Diabetes & Endocrinology
state: California
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Torrance
country: United States
facility: SoCal Diabetes
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research
state: California
city: Aurora
country: United States
facility: Barbara Davis Center
state: Colorado
city: Tampa
country: United States
facility: University of South Florida Diabetes Center
state: Florida
city: Atlanta
country: United States
facility: Atlanta Diabetes Associates
state: Georgia
city: Roswell
country: United States
facility: Endocrine Research Solutions
state: Georgia
city: Idaho Falls
country: United States
facility: Rocky Mountain Diabetes
state: Idaho
city: Indianapolis
country: United States
facility: Indiana University Health Riley Hospital for Children
state: Indiana
city: Des Moines
country: United States
facility: IDERC
state: Iowa
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Bloomfield Hills
country: United States
facility: Grunberger Diabetes Institute
state: Michigan
city: Minneapolis
country: United States
facility: Initernational Diabetes Center
state: Minnesota
city: Minneapolis
country: United States
facility: International Diabetes Center
state: Minnesota
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University St. Louis
state: Missouri
city: Syracuse
country: United States
facility: SUNY Upstate Medical University
state: New York
city: Sioux Falls
country: United States
facility: Sanford Health
state: South Dakota
city: Austin
country: United States
facility: Texas Diabetes & Endocrinology
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Glandular Disease Clinic, P.A.
state: Texas
city: Renton
country: United States
facility: Rainier Clinical Research
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: New Westminster
country: Canada
facility: Westminster Endocrine & Diabetes Research Society
state: British Columbia
city: Ottawa
country: Canada
facility: Children's Hospital of Eastern Ontario
city: Paris
country: France
facility: Hôpital Necker Enfants Malades
city: Pierre-Bénite
country: France
facility: HCL - Lyon Sud
city: Hannover
country: Germany
facility: Diabeteszentrum für Kinder und Jugendliche, Kinder- und Jugendkrankenhaus Auf der Bult
city: Brescia
country: Italy
facility: A.S.S.T. Spedali Civili
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research
city: Dunedin
country: New Zealand
facility: Dunedin Public Hospital
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Örebro
country: Sweden
facility: Dept Internal Medicine, Örebro University Hospital
city: Cambridge
country: United Kingdom
facility: Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital
Study officials:
References: