Safety Evaluation of the Hybrid Closed Loop (HCL) System in Pediatric Subjects With Type 1 Diabetes

This study is a single-arm, multi-center, Home and Hotel Clinical Investigation in pediatric subjects with type 1 diabetes on insulin pump therapy. The purpose of this study is to demonstrate that the closed loop algorithm is safe as part of the overall system, and to assess the PLGM feature in 7-13 years old subjects.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Insulin Pump

Detailed Description

The study will proceed as follows:

Run-in Period - General:

A total of up to 200 subjects (age 2-13) will be enrolled at up to 15 investigational centers (14 in the US, 1 EMEA) in order to reach 120 subjects who will complete the HCL study.

Study Period - At Home:

Following the two week run-in period using the Study Pump (670G), all subjects (age 2-13) will participate in a 3-month study period.

Study Period - Hotel Study Subjects (age 7-13) will participate in a Hotel study (6 days, 5 nights), with the remainder of the study period to be spent at home. Subjects 2-6 years of age are not required to participate in a hotel study. Instead, they will participate in an out-of-home study for 5 consecutive days, 4-6 hours per day.

Continued Access Program Subjects will be given the opportunity to extend use of their study devices for a period of up to 3 years . If subjects choose to participate in the continuation period, they will retain the study devices at the end of study period visit or receive them back in the event they have been returned to study staff already.

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Tel Aviv, Israel
    • Sheba Medical Center
• United States
  • California
    • Escondido, California, United States, 92025
      • AMCR Institute
    • Palo Alto, California, United States, 94305
      • Stanford Hospital and Clinics
    • Torrance, California, United States, 90505
      • SoCal Diabetes
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Barbara Davis Center
  • Florida
    • Jacksonville, Florida, United States, 32207
      • Nemours Children's Clinic
    • Tampa, Florida, United States, 33620
      • University of South Florida - USF Health
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Atlanta Diabetes Associates
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Diabetes and Osteoporosis Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 13 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

General Inclusion Criteria

1. Subject is age 2-13 years at time of screening
2. Subject has 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

3. Subject age 2-6 years has a clinical diagnosis of type 1 diabetes for 3 months 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 must have a minimum daily insulin requirement (Total Daily Dose) of greater than or equal to 8 units
5. Subjects 7-13: Subjects and their parent(s)/guardian(s) are willing to participate in an overnight visit at the end of the run-in period.
6. Subject 7-13 years of age and their parent(s)/guardian(s) are willing to participate in a hotel study for the specified duration of hotel stay.
7. Subject 2-6 years of age and their parent(s)/guardian(s) are willing to participate in an extended visit during the study period to perform Frequent Sample Testing.
8. Subject must have companion 18 years or older who will sleep in the same dwelling place every night during the study period. This requirement may be verified by subject report at screening visit.
9. Subject is willing to perform ≥ 4 finger stick blood glucose measurements daily
10. Subject is willing to perform required sensor calibrations
11. Subject is willing to wear the system continuously throughout the study
12. Subject has a Glycosylated hemoglobin (A1C) value less than 10.0% (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. A1C testing must follow National Glycohemoglobin Standardization Program (NGSP) standards.
13. 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.
14. Subject 7 -13 years of age has had pump therapy for greater than 6 months prior to screening (with or without CGM experience)
15. Subject 2-6 years of age has had pump therapy for greater than 90 days prior to screening (with or without CGM experience)
16. Subjects and their parent(s)/guardian(s) are 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
17. If subject has celiac disease, it has been adequately treated as determined by the investigator

18. Subjects and their parent(s)/guardian(s) are 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)
19. Subjects and their parent(s)/guardian(s)/companions must be able to speak and be literate in English as verified by the investigator

Exclusion Criteria:

1. Subject has a history of 2 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 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, dermatitis herpetiformis, rash, Staphylococcus infection)
4. 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.
5. Subject has a cardiovascular condition which the investigator determines should exclude the subject, i.e. ventricular rhythm disturbance, hypertrophic cardiomyopathy
6. Subject is being treated for hyperthyroidism at time of screening
7. Subject has diagnosis of adrenal insufficiency
8. Subject 7-13 years of age has had DKA in the 6 months prior to screening visit.
9. Subject 2-6 years of age has had DKA in the 3 months prior to screening visit
10. Subject has taken any oral, injectable, or intravenous (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
11. 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
12. Subject 7-13 years of age has been hospitalized or has visited the ER in the 6 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes
13. Subject 2-6 years of age has been hospitalized or has visited the ER in the 3 months prior to screening resulting in a primary diagnosis of uncontrolled diabetes
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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hybrid closed loop; All subjects will be wearing the MMT-670G insulin pump, using it with the closed loop algorithm	Device: Insulin Pump; Closed Loop Algorithm; Other Names: MMT-670G

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age 2-13 Years Old Subjects Change in A1C	Descriptive analysis of change in A1C from baseline to end of 3-month study period	Baseline and end of 3-month study period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age 2-13 Years Old Subjects Mean Change in % of Time in Euglycemia (70-180 mg/dL)	mean change in % of time in Euglycemia (70-180 mg/dL) from baseline to 3 months study period	baseline and 3 months
Age 2-13 Years Old Subjects Mean Change in % of Time in Hyperglycemia (> 180 mg/dL)	mean change in % of time in hyperglycemia (> 180 mg/dL) from baseline to 3 months study period	baseline and 3 months
Age 2-13 Years Old Subjects Mean Change in % of Time in Hypoglycemia (<70 mg/dL)	mean change in % of time in hypoglycemia (< 70 mg/dL) from baseline to 3 months study period	baseline and 3 months
Age 2-13 Years Old - Number of Severe Hypoglycemic Event	Number of severe hypoglycemic events occurred during 3-month study period.	3 months
Age 2-13 Years Old - Number of Diabetic Ketoacidosis (DKA) Event	Number of Diabetic Ketoacidosis (DKA) events occurred during 3-month study period.	3 months
Age 7-13 Years Old Subjects PLGM Performance - Event Rate Without Hypoglycemia at YSI-FST <=65 mg/dL	Event rate without Hypoglycemia at YSI-FST <=65 mg/dL among 105 subjects who underwent the PLGM experiments. The event rate without hypoglycemia is the number of experiments without hypoglycemia/total number of experiments and hypoglycemic events are defined based on the occurrence of 2 or more continuous YSI-FST <= 65mg/dL during in-clinic procedures.	Up to 12 hours after the start of PLGM period

Collaborators and Investigators

• Sponsor: Medtronic Diabetes

Publications and helpful links

General Publications

• Forlenza GP, Ekhlaspour L, DiMeglio LA, Fox LA, Rodriguez H, Shulman DI, Kaiserman KB, Liljenquist DR, Shin J, Lee SW, Buckingham BA. Glycemic outcomes of children 2-6 years of age with type 1 diabetes during the pediatric MiniMed 670G system trial. Pediatr Diabetes. 2022 May;23(3):324-329. doi: 10.1111/pedi.13312. Epub 2022 Jan 31.
• Forlenza GP, Pinhas-Hamiel O, Liljenquist DR, Shulman DI, Bailey TS, Bode BW, Wood MA, Buckingham BA, Kaiserman KB, Shin J, Huang S, Lee SW, Kaufman FR. Safety Evaluation of the MiniMed 670G System in Children 7-13 Years of Age with Type 1 Diabetes. Diabetes Technol Ther. 2019 Jan;21(1):11-19. doi: 10.1089/dia.2018.0264. Epub 2018 Dec 26.

Study record dates

Study Major Dates

• Study Start (Actual): April 18, 2016
• Primary Completion (Actual): November 28, 2018
• Study Completion (Actual): February 1, 2021

Study Registration Dates

• First Submitted: January 16, 2016
• First Submitted That Met QC Criteria: January 16, 2016
• First Posted (Estimate): January 21, 2016

Study Record Updates

• Last Update Posted (Actual): January 26, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin
• Other Study ID Numbers: CEP 302

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No