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

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

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)

Study Overview

• Status: Recruiting
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: 670G and 770G Insulin Pump; Device: Subject's Current Diabetes Therapy

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.

• Study Type: Interventional
• Enrollment (Estimated): 280
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Troub; Phone Number: 818-576-3142; Email: thomas.troub@medtronic.com
• Study Contact Backup: Name: Briggitte Marinos; Phone Number: 818-576-5373; Email: briggitte.s.marinos@medtronic.com

Study Locations

• Canada
  • Ottawa, Canada, K1H 8L1
    • Completed
    • Children's Hospital of Eastern Ontario
  • British Columbia
    • New Westminster, British Columbia, Canada, V3L 3W5
      • Completed
      • Westminster Endocrine & Diabetes Research Society
• France
  • Paris, France, 75015
    • Completed
    • Hopital Necker Enfants Malades
  • Pierre-Bénite, France, 69495
    • Completed
    • HCL - Lyon Sud
• Germany
  • Hannover, Germany, 30173
    • Completed
    • Diabeteszentrum für Kinder und Jugendliche, Kinder- und Jugendkrankenhaus Auf der Bult
• Italy
  • Brescia, Italy, 25028
    • Completed
    • A.S.S.T. Spedali Civili
• New Zealand
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Clinical Research
    • Contact: Antony Watson; Email: antony.watson@otago.ac.nz
    • Principal Investigator: Martin de Bock, MD
  • Dunedin, New Zealand, 9016
    • Recruiting
    • Dunedin Public Hospital
    • Contact: Alisa Boucsein; Email: a.boucsein@otago.ac.nz
    • Principal Investigator: Benjamin Wheeler, MD
• Spain
  • Sevilla, Spain
    • Completed
    • Hospital Universitario Virgen Del Rocio
• Sweden
  • Örebro, Sweden, SE-70185
    • Completed
    • Dept Internal Medicine, Örebro University Hospital
• United Kingdom
  • Cambridge, United Kingdom
    • Completed
    • Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital
• United States
  • California
    • La Jolla, California, United States, 92037
      • Completed
      • Scripps Health System
    • Palo Alto, California, United States, 94304
      • Completed
      • Stanford University
    • Sacramento, California, United States, 95821
      • Active, not recruiting
      • Center of Excellence in Diabetes & Endocrinology
    • Santa Barbara, California, United States, 93105
      • Completed
      • Sansum Diabetes Research Institute
    • Torrance, California, United States, 90505
      • Completed
      • SoCal Diabetes
    • Walnut Creek, California, United States, 94598
      • Completed
      • Diablo Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Completed
      • Barbara Davis Center
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Withdrawn
      • Yale School of Medicine
  • Florida
    • Tampa, Florida, United States, 33612
      • Recruiting
      • University of South Florida Diabetes Center
      • Contact: Janet Rodriguez; Phone Number: 813-974-5499; Email: janetrodriguez@health.usf.edu
      • Principal Investigator: Dorothy Shulman, MD
  • Georgia
    • Atlanta, Georgia, United States, 30318
      • Completed
      • Atlanta Diabetes Associates
    • Roswell, Georgia, United States, 30076
      • Completed
      • Endocrine Research Solutions
  • Idaho
    • Idaho Falls, Idaho, United States, 93404
      • Recruiting
      • Rocky Mountain Diabetes
      • Principal Investigator: David Liljenquist, MD
      • Contact: Joanne Malone; Phone Number: 208-522-6005; Email: joann@idahomed.com
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Completed
      • Indiana University Health Riley Hospital for Children
  • Iowa
    • Des Moines, Iowa, United States, 50265
      • Active, not recruiting
      • IDERC
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Completed
      • University of Michigan
    • Bloomfield Hills, Michigan, United States, 48302
      • Completed
      • Grunberger Diabetes Institute
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Completed
      • Initernational Diabetes Center
    • Minneapolis, Minnesota, United States, 55416
      • Active, not recruiting
      • International Diabetes Center
    • Rochester, Minnesota, United States, 55905
      • Completed
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Completed
      • Washington University St. Louis
  • New York
    • Syracuse, New York, United States, 13210
      • Completed
      • SUNY Upstate Medical University
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57104
      • Completed
      • Sanford Health
  • Texas
    • Austin, Texas, United States, 78731
      • Completed
      • Texas Diabetes & Endocrinology
    • Houston, Texas, United States, 77030
      • Withdrawn
      • Texas Children's Hospital / Baylor University
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • Diabetes and Glandular Disease Clinic, P.A.
      • Contact: Terri Ryan; Phone Number: 210-614-8612; Email: terri.ryan@dgdclinic.com
      • Principal Investigator: Mark S Kipnes, MD
  • Washington
    • Renton, Washington, United States, 98057
      • Completed
      • Rainier Clinical Research
    • Seattle, Washington, United States, 98105
      • Completed
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hybrid Closed Loop Arm; 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; Medtronic 670G and 770G Hybrid Closed Loop Systems
Active Comparator: Control Arm; 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; Subject will use current diabetes therapy: CSII (Continuous Subcutaneous Insulin Infusion), MDI (Multiple Daily Injections) or SAP (Sensor Augmented Pump).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Medtronic Diabetes

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2017
• Primary Completion (Estimated): March 1, 2024
• Study Completion (Estimated): September 1, 2024

Study Registration Dates

• First Submitted: April 19, 2016
• First Submitted That Met QC Criteria: April 21, 2016
• First Posted (Estimated): April 22, 2016

Study Record Updates

• Last Update Posted (Actual): January 22, 2024
• Last Update Submitted That Met QC Criteria: January 18, 2024
• Last Verified: January 1, 2024

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 304

Plan for Individual participant data (IPD)

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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes