Clinical trial NCT04196140: Pivotal Omnipod Horizon™ Automated Glucose Control System
Official title: Evaluating the Safety and Effectiveness of the Omnipod Horizon™ Automated Glucose Control System in Patients With Type 1 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Keywords: T1D
Omnipod
Lead sponsor: Insulet Corporation
Sponsor class: INDUSTRY
First posted: 2019-12-12
Enrollment: 240
Sex: ALL
Minimum age (years): 6
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a single-arm, multi-center, prospective clinical study.
Primary purpose: TREATMENT

Brief summary: Subjects will undergo a 14-day outpatient, standard therapy phase during which sensor and insulin data will be collected. This will be followed by a 94-day (13-week) hybrid closed-loop phase conducted in an outpatient setting and an optional 12-month extension phase.

Detailed description: The study schedule will consist of a standard therapy data collection phase followed by a hybrid closed-loop phase.

Subjects will undergo a 14-day outpatient, standard therapy phase (Phase 1 or ST) during which sensor and insulin data will be collected. Subjects, or their caregivers, will manage their diabetes at home per their usual routine using the study continuous glucose monitoring system (CGM) and remain on current multiple daily injections (MDI) or pump therapy. This will be followed by a 94-day (13-week) hybrid closed-loop phase (Phase 2), conducted in an outpatient setting where subjects, or their caregivers, will manage their diabetes at home using the Omnipod Horizon™ Automated Glucose Control System. After completing the 94-day hybrid closed-loop phase, subjects will have the option to continue using the system for an additional 12 months (Phase 3).

During the hybrid closed-loop phase, there will be supervised exercise challenges. A subset of subjects will participate in 5-days of supervised Meal and Exercise challenges. A subset of subjects will participate in 3-days of supervised HypoProtect Exercise challenges where comparisons were made between exercising in Automated Mode vs initiating HypoProtect 60 minutes prior to exercise vs initiating HypoProtect 30 minutes prior to exercise.

The hybrid closed-loop phase will begin on Study Day 1.

Eligibility criteria: Inclusion Criteria:

1. Age at time of consent/assent 6-70 years
2. Subjects aged \< 18 years must be living with parent/legal guardian
3. Diagnosed with type 1 diabetes for at least 6 months. Diagnosis is based on investigator's clinical judgment
4. Deemed appropriate for pump therapy per investigator's assessment taking into account previous history of severe hypoglycemic and hyperglycemic events, and other comorbidities
5. Investigator has confidence that the subject can successfully operate all study devices and is capable of adhering to the protocol
6. Willing to use only the following types of insulin during the study: Humalog, Novolog, Admelog or Apidra during the study
7. Must be willing to travel to and participate in meal and exercise challenges during 5-days of the hybrid closed-loop phase
8. Willing to wear the system continuously throughout the study
9. A1C \<10% at screening visit
10. Must be willing to use the Dexcom App on the Omnipod Horizon™ Personal Diabetes Manager (PDM) as the sole source of Dexcom data (with the exception of the Dexcom Follow App) during the hybrid closed-loop phase
11. Subjects scoring ≥ 4 on the Clarke Questionnaire must agree to have an overnight companion, defined as someone who resides in the same home or building as the study subject and who can be available overnight
12. Able to read and speak English fluently
13. Willing and able to sign the Informed Consent Form (ICF) and/or has a parent/guardian willing and able to sign the ICF. Assent will be obtained from pediatric and adolescent subjects aged \< 18 years per State requirements.

Exclusion Criteria:

1. A medical condition, which in the opinion of the investigator, would put the subject at an unacceptable safety risk
2. History of severe hypoglycemia in the past 6 months
3. History of DKA in the past 6 months, unrelated to an intercurrent illness, infusion set failure or initial diagnosis
4. Diagnosed with sickle cell disease
5. Diagnosed with hemophilia or any other bleeding disorders
6. Plans to receive blood transfusion over the course of the study
7. Currently diagnosed with anorexia nervosa or bulimia
8. Acute or chronic kidney disease (e.g. estimated GFR \< 45) or currently on hemodialysis
9. History of adrenal insufficiency
10. Has taken oral or injectable steroids within the past 8-weeks or plans to take oral or injectable steroids during the course of the study
11. Unable to tolerate adhesive tape or has any unresolved skin condition in the area of sensor or pump placement
12. Plans to use insulin other than U-100 insulin intended for use in the study device during the course of the study
13. Use of non-insulin anti-diabetic medication other than metformin (e.g. GLP1 agonist, SGLT2 inhibitor, DPP-4 inhibitor, pramlintide)
14. Current or known history of coronary artery disease that is not stable with medical management, including unstable angina, or angina that prevents moderate exercise despite medical management, or a history of myocardial infarction, percutaneous coronary intervention, or coronary artery bypass grafting within the previous 12-months.
15. For subjects \>50 years old or with diabetes duration \>20 years, abnormal electrocardiogram consistent with increased risk of arrhythmia, ischemia, or prolonged QTc interval (\> 450 ms)
16. Thyroid Stimulating Hormone (TSH) is outside of normal range with clinical signs of hypothyroidism or hyperthyroidism
17. Pregnant or lactating, or is a woman of childbearing potential and not on acceptable form of birth control (acceptable includes abstinence, condoms, oral/injectable contraceptives, IUD or implant)
18. Participation in another clinical study using an investigational drug or device other than the Omnipod Horizon™ Automated Glucose Control System within the preceding 30-days or intends to participate during the study period
19. Unable to follow clinical protocol for the duration of the study or is otherwise deemed unacceptable to participate in the study per the investigator's clinical judgment

Primary outcomes:
measure: Incidence Rate of Severe Hypoglycemia (Events Per Person Months)
timeFrame: Phase 2 hybrid closed-loop (94 days)
measure: Incidence Rate of Diabetic Ketoacidosis (DKA) (Events Per Person Months)
timeFrame: Phase 2 hybrid closed-loop (94 days)
measure: Glycated Hemoglobin (A1C)
timeFrame: 6 weeks continuous Phase 2 participation compared to baseline
measure: Time in Range 70-180 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days)
Secondary outcomes:
measure: Percent of Time >180 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days)
measure: Percent of Time <70 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) compared to Phase 1 standard therapy (14 days)
measure: Glycated Hemoglobin (A1C)
timeFrame: at least 6 weeks and at least 8 weeks of continuous Phase 2 participation, end of Phase 2 (94 days), 6 months (180 days) and end of Phase 3 (270 days)
measure: Mean Glucose
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time in Range 70-180 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time in Range 70-140 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time >180 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time ≥ 250 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time ≥ 300 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time < 70 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent of Time < 54 mg/dL
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Standard Deviation (of Glucose)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percent Coefficient of Variation (of Glucose)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to Phase 1 standard therapy (14 days) during the day, overnight, and overall
measure: Percentage of Time in Hybrid Closed-loop as Proportion of Overall Device Usage Time
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 (270 days)
measure: Percent Glucose Management Indicator (% GMI)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Insulin (TDI) (Units)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Insulin (TDI) (Units/kg)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Basal Insulin (Units)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Basal Insulin (Units/kg)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Bolus Insulin (Units)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Total Daily Bolus Insulin (Units/kg)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to the Phase 1 standard therapy (14 days)
measure: Body Mass Index (BMI) (kg/m^2)
timeFrame: Phase 2 hybrid closed-loop (94 days) and Phase 3 hybrid closed-loop (270 days) compared to baseline
Other outcomes:
measure: Incidence Rate of Hypoglycemia (<70 mg/dL Confirmed by BG)
timeFrame: HypoProtect compared to standard Omnipod 5 system use (3-day exercise challenge)
measure: Number of Hypoglycemic Events (<70 mg/dL Confirmed by BG)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Area Under the Curve (AUC) Less Than 70 mg/dL (Based on CGM Value)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Minimum Continuous Glucose Monitor Value (Nadir Glucose)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Area Under the Curve (AUC) Greater Than 180 mg/dL (Based on CGM Value)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Mean Absolute Decrease in Glucose (Based on CGM Value, From Start of Exercise to Nadir Glucose)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Carbohydrates Consumed During Exercise (Grams)
timeFrame: HypoProtect compared to Automated Mode (3-day exercise challenge)
measure: Mean Glucose
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time in Range 70-180 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time > 180 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time ≥ 250 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time ≥ 300 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time < 70 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Percent of Time < 54 mg/dL
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Standard Deviation (of Glucose)
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
measure: Coefficient of Variation (of Glucose)
timeFrame: Automated Mode compared to HypoProtect use during 70-minute exercise session and at 4-, 12-, and 24-hours post-exercise
Locations:
city: Palo Alto
country: United States
facility: Stanford University
state: California
city: Santa Barbara
country: United States
facility: Sansum Diabetes Research Institute
state: California
city: Denver
country: United States
facility: University of Colorado Denver
state: Colorado
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Atlanta Diabetes
state: Georgia
city: Macon
country: United States
facility: East Coast Institute for Research
state: Georgia
city: Evanston
country: United States
facility: Northwestern University
state: Illinois
city: West Des Moines
country: United States
facility: Iowa Diabetes
state: Iowa
city: Boston
country: United States
facility: Joslin Diabetes Center
state: Massachusetts
city: Saint Louis Park
country: United States
facility: International Diabetes Center
state: Minnesota
city: New York
country: United States
facility: Mount Sinai
state: New York
city: Syracuse
country: United States
facility: SUNY Syracuse
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: Stanford University
name: Bruce Buckingham, MD
role: STUDY_CHAIR
affiliation: University of Virginia
name: Sue Brown, MD
role: STUDY_CHAIR
References:
citation: Polonsky WH, Hood KK, Levy CJ, MacLeish SA, Hirsch IB, Brown SA, Bode BW, Carlson AL, Shah VN, Weinstock RS, Bhargava A, Jones TC, Aleppo G, Mehta SN, Laffel LM, Forlenza GP, Sherr JL, Huyett LM, Vienneau TE, Ly TT; Omnipod 5 Research Group. How introduction of automated insulin delivery systems may influence psychosocial outcomes in adults with type 1 diabetes: Findings from the first investigation with the Omnipod(R) 5 System. Diabetes Res Clin Pract. 2022 Aug;190:109998. doi: 10.1016/j.diabres.2022.109998. Epub 2022 Jul 16.
citation: Brown SA, Forlenza GP, Bode BW, Pinsker JE, Levy CJ, Criego AB, Hansen DW, Hirsch IB, Carlson AL, Bergenstal RM, Sherr JL, Mehta SN, Laffel LM, Shah VN, Bhargava A, Weinstock RS, MacLeish SA, DeSalvo DJ, Jones TC, Aleppo G, Buckingham BA, Ly TT; Omnipod 5 Research Group. Multicenter Trial of a Tubeless, On-Body Automated Insulin Delivery System With Customizable Glycemic Targets in Pediatric and Adult Participants With Type 1 Diabetes. Diabetes Care. 2021 Jul;44(7):1630-1640. doi: 10.2337/dc21-0172. Epub 2021 Jun 7.