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

• ClinicalTrials.gov Identifier: NCT02748018
• Recruitment Status: Recruiting
• First Posted: April 22, 2016
• Last Update Posted: November 17, 2022
• Sponsor: Medtronic Diabetes
• Information provided by (Responsible Party): Medtronic Diabetes

Study Description

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)

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: 670G and 770G Insulin Pump; Device: Subject's Current Diabetes Therapy	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 280 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: May 25, 2017
• Estimated Primary Completion Date: July 2023
• Estimated Study Completion Date: January 2024

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. CSII Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
   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%
2. CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
   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%
3. MDI Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
   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%
4. MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
   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%
5. SAP Cohort: change of A1C (∆A1C) for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
   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. SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
   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%

Secondary Outcome Measures :

1. CSII Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
   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%
2. CSII Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
   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%
3. CSII Cohort: Time in Hypoglycemic Range during Night for all subjects [ Time Frame: 6 months ]
   CSII Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects
4. CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects [ Time Frame: 6 months ]
   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
5. CSII Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects [ Time Frame: 6 months ]
   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. CSII Cohort: Time in Hypoglycemic Range during Day and Night for all subjects [ Time Frame: 6 months ]
   CSII Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects
7. CSII Cohort: Change in A1C for all subjects [ Time Frame: 6 months ]
   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
8. MDI Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
   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%
9. MDI Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
   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%
10. MDI Cohort: Time in Hypoglycemic Range during Night for all subjects [ Time Frame: 6 months ]
    MDI Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects
11. MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects [ Time Frame: 6 months ]
    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
12. MDI Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects [ Time Frame: 6 months ]
    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
13. MDI Cohort: Time in Hypoglycemic Range during Day and Night for all subjects [ Time Frame: 6 months ]
    MDI Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects
14. MDI Cohort: Change in A1C for all subjects [ Time Frame: 6 months ]
    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
15. SAP Cohort: Time in Hypoglycemic Range for subjects with baseline A1c > 8% [ Time Frame: 6 months ]
    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%
16. SAP Cohort: Change in A1C (∆A1C) for subjects with baseline A1c ≤ 8% [ Time Frame: 6 months ]
    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%
17. SAP Cohort: Time in Hypoglycemic Range during Night for all subjects [ Time Frame: 6 months ]
    SAP Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Night for all subjects
18. SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Night for all subjects [ Time Frame: 6 months ]
    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
19. SAP Cohort: Time in Target Range 70mg/dL (3.9mmol/L) - 180 mg/dL (10.0mmol/L) during Day and Night for all subjects [ Time Frame: 6 months ]
    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
20. SAP Cohort: Time in Hypoglycemic Range during Day and Night for all subjects [ Time Frame: 6 months ]
    SAP Cohort: Time with SG below 70 mg/dL (3.9mmol/L) during Day and Night for all subjects
21. SAP Cohort: Change in A1C for all subjects [ Time Frame: 6 months ]
    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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Thomas Troub; 818-576-3142; thomas.troub@medtronic.com

Contact: Briggitte Marinos; 818-576-5373; briggitte.s.marinos@medtronic.com

Locations

United States, California

Scripps Health System; Completed

La Jolla, California, United States, 92037

Stanford University; Completed

Palo Alto, California, United States, 94304

Center of Excellence in Diabetes & Endocrinology; Recruiting

Sacramento, California, United States, 95821

Contact: Natalie Marlen 916-426-1902 capitolcts@gmail.com

Principal Investigator: Gnanagurudasan Prakasam, MD

Sansum Diabetes Research Institute; Completed

Santa Barbara, California, United States, 93105

SoCal Diabetes; Completed

Torrance, California, United States, 90505

Diablo Clinical Research; Active, not recruiting

Walnut Creek, California, United States, 94598

United States, Colorado

Barbara Davis Center; Completed

Aurora, Colorado, United States, 80045

United States, Connecticut

Yale School of Medicine; Withdrawn

New Haven, Connecticut, United States, 06511

United States, Florida

University of South Florida Diabetes Center; Recruiting

Tampa, Florida, United States, 33612

Contact: Janet Rodriguez 813-974-5499 janetrodriguez@health.usf.edu

Principal Investigator: Dorothy Shulman, MD

United States, Georgia

Atlanta Diabetes Associates; Completed

Atlanta, Georgia, United States, 30318

Endocrine Research Solutions; Recruiting

Roswell, Georgia, United States, 30076

Contact: Jessica Tapia 678-878-4750 jessiet62@gmail.com

Principal Investigator: John Reed, MD

United States, Idaho

Rocky Mountain Diabetes; Recruiting

Idaho Falls, Idaho, United States, 93404

Contact: Joanne Malone 208-522-6005 joann@idahomed.com

Principal Investigator: David Liljenquist, MD

United States, Indiana

Indiana University Health Riley Hospital for Children; Completed

Indianapolis, Indiana, United States, 46202

United States, Iowa

IDERC; Recruiting

Des Moines, Iowa, United States, 50265

Contact: Lisa Borg 515-643-5118 lborg@iowadiabetes.com

Principal Investigator: Anuj Bhargava, MD

United States, Michigan

University of Michigan; Recruiting

Ann Arbor, Michigan, United States, 48109

Contact: Cindy Plunkett, RN 734-936-8065 cplunket@med.umich.edu

Principal Investigator: Rodica Pop-Busui, MD

Grunberger Diabetes Institute; Completed

Bloomfield Hills, Michigan, United States, 48302

United States, Minnesota

Initernational Diabetes Center; Completed

Minneapolis, Minnesota, United States, 55416

International Diabetes Center; Recruiting

Minneapolis, Minnesota, United States, 55416

Contact: Diane Whipple 952-993-2739 diane.whipple@parknicollet.com

Principal Investigator: Anders Carlson, MD

Mayo Clinic; Recruiting

Rochester, Minnesota, United States, 55905

Contact: Corey Reid Reid.Corey@mayo.edu

Principal Investigator: Yogish Kudva, MD

United States, Missouri

Washington University St. Louis; Completed

Saint Louis, Missouri, United States, 63110

United States, New York

SUNY Upstate Medical University; Completed

Syracuse, New York, United States, 13210

United States, South Dakota

Sanford Health; Completed

Sioux Falls, South Dakota, United States, 57104

United States, Texas

Texas Diabetes & Endocrinology; Completed

Austin, Texas, United States, 78731

Texas Children's Hospital / Baylor University; Withdrawn

Houston, Texas, United States, 77030

Diabetes and Glandular Disease Clinic, P.A.; Recruiting

San Antonio, Texas, United States, 78229

Contact: Terri Ryan 210-614-8612 terri.ryan@dgdclinic.com

Principal Investigator: Mark S Kipnes, MD

United States, Washington

Rainier Clinical Research; Completed

Renton, Washington, United States, 98057

University of Washington; Completed

Seattle, Washington, United States, 98105

Canada, British Columbia

Westminster Endocrine & Diabetes Research Society; Completed

New Westminster, British Columbia, Canada, V3L 3W5

Canada

Children's Hospital of Eastern Ontario; Recruiting

Ottawa, Canada, K1H 8L1

Contact: Brenda Bradley bbradley@cheo.on.ca

Principal Investigator: Margaret Lawson, MD

France

Hôpital Necker Enfants Malades; Completed

Paris, France, 75015

HCL - Lyon Sud; Completed

Pierre-Bénite, France, 69495

Germany

Diabeteszentrum für Kinder und Jugendliche, Kinder- und Jugendkrankenhaus Auf der Bult; Completed

Hannover, Germany, 30173

Italy

A.S.S.T. Spedali Civili; Completed

Brescia, Italy, 25028

New Zealand

New Zealand Clinical Research; Recruiting

Christchurch, New Zealand, 8011

Contact: Antony Watson antony.watson@otago.ac.nz

Principal Investigator: Martin de Bock, MD

Dunedin Public Hospital; Recruiting

Dunedin, New Zealand, 9016

Contact: Alisa Boucsein a.boucsein@otago.ac.nz

Principal Investigator: Benjamin Wheeler, MD

Spain

Hospital Universitario Virgen del Rocío; Completed

Sevilla, Spain

Sweden

Dept Internal Medicine, Örebro University Hospital; Completed

Örebro, Sweden, SE-70185

United Kingdom

Cambridge University Hospitals NHS Foundation Trust - Addenbrooke's Hospital; Completed

Cambridge, United Kingdom

Sponsors and Collaborators

Medtronic Diabetes

More Information

• Responsible Party: Medtronic Diabetes
• ClinicalTrials.gov Identifier: NCT02748018
• Other Study ID Numbers: CEP 304
• First Posted: April 22, 2016
• Last Update Posted: November 17, 2022
• Last Verified: November 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Insulin; Hypoglycemic Agents; Physiological Effects of Drugs