Early Feasibility Study of Zone-MPC and HMS With DiAs in the Outpatient Setting

Early Feasibility Study of a Zone-Model Predictive Control (MPC) Controller and a Health Monitoring System (HMS) With the Diabetes Assistant (DiAS) in the Outpatient Setting

This is a feasibility study of an artificial pancreas (AP) system with our previously validated Zone-MPC and Health Monitoring System (HMS) algorithms (ClinicalTraisl.gov: NCT01929798) integrated into the Diabetes Assistant (DiAs) system.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Device: CGM and Insulin Pump; Device: Closed-Loop Control System

Detailed Description

This is a feasibility study of an artificial pancreas (AP) system with our previously validated Zone-MPC and Health Monitoring System (HMS) algorithms (ClinicalTraisl.gov: NCT01929798) integrated into the Diabetes Assistant (DiAs) system. The system will be evaluated on 2-3 subjects per site (n=6-9 subjects) for 2 weeks at 3 different sites (William Sansum Diabetes Center, University of Virginia, and Mayo Clinic, Rochester, MN). Basal rates will be adjusted in a run-to-run manner by study physicians prior to the closed-loop phase for a maximum of 3 weeks. Subjects will then complete 2 weeks at home use of the Zone-MPC/HMS system using the DIAs platform for a closed-loop feasibility trial. The purpose of this pilot study is to establish that safe day-and-night use of the Zone-MPC/HMS system integrated into the DiAs is achievable in the home environment, to analyze and learn to improve upon the run-to- run optimization process, and to collect efficacy data to inform a future larger study.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Barbara, California, United States, 93111
      • William Sansum Diabetes Center
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • University of Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis, based on investigator assessment, of type 1 diabetes for at least one year and using insulin for at least 1 year and an insulin pump for at least 6 months
• Willing to wear the study CGM device for the duration of the study
• Age ≥21 to <65 years
• HbA1c <10.0%; if HbA1c <6.0% then total daily insulin must be ≥0.5 U/kg
• For females, not currently known to be pregnant If female and sexually active, must agree to use a form of contraception to prevent pregnancy while a participant in the study. A negative urine pregnancy test will be required for all premenopausal women who are not surgically sterile. Subjects who become pregnant will be discontinued from the study.
• Demonstration of proper mental status and cognition for the study
• Currently using insulin-to-carbohydrate ratio to calculate meal bolus sizes
• Hypoglycemia awareness as demonstrated by a Clarke Hypoglycemia Unawareness score of 2 or lower
• Access to internet and cell phone service at home, and a computer for downloading device data
• Availability of care partner committed to participating in training activities, knowledgeable at all times of the participant's location, and being present and available to provide assistance when system is being used at night
• Commitment to maintaining uninterrupted availability via cell phone and avoiding any overnight travel for the duration the period using the closed-loop system
• An understanding of and willingness to follow the protocol and sign the informed consent

Exclusion Criteria:

• Admission for diabetic ketoacidosis in the 12 months prior to enrollment
• Severe hypoglycemia resulting in seizure or loss of consciousness in the 12 months prior to enrollment
• History of a seizure disorder (except hypoglycemic seizure), unless written clearance is received from a neurologist
• Coronary artery disease or heart failure, unless written clearance is received from a cardiologist
• History of cardiac arrhythmia (except for benign premature atrial contractions and benign premature ventricular contractions which are permitted)
• Cystic fibrosis

• A known medical condition that in the judgment of the investigator might interfere with the completion of the protocol such as the following examples:

  • Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian)
  • Presence of a known adrenal disorder
  • Abnormal liver function test results (Transaminase >2 times the upper limit of normal); testing required for subjects taking medications known to affect liver function or with diseases known to affect liver function
  • Abnormal renal function test results (calculated GFR <60 mL/min/1.73m2); testing required for subjects with diabetes duration of greater than 5 years post onset of puberty
  • Active gastroparesis
  • If on antihypertensive, thyroid, anti-depressant or lipid lowering medication, lack of stability on the medication for the past 2 months prior to enrollment in the study
  • Uncontrolled thyroid disease (TSH undetectable or >10 mlU/L); testing required within three months prior to admission for subjects with a goiter or who are on thyroid hormone replacement, and within one year otherwise
  • Abuse of alcohol or recreational drugs
  • Infectious process not anticipated to resolve prior to study procedures (e.g. meningitis, pneumonia, osteomyelitis)
• A recent injury to body or limb, muscular disorder, use of any medication, any carcinogenic disease, or other significant medical disorder if that injury, medication or disease in the judgment of the investigator will affect the completion of the protocol

• Current use of the following drugs and supplements:

  • Acetaminophen
  • Any medication being taken to lower blood glucose, such as Pramlintide, Metformin,GLP-1 Analogs such as Liraglutide, and nutraceuticals intended to lower blood glucose
  • Beta blockers
  • Oral or injectable glucocorticoids
  • Any other medication that the investigator believes is a contraindication to the subject's participation

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sensor-Augmented Pump Open-Loop Care (Week 1); The subjects Sensor-Augmented Pump Open-Loop Care for the first week of the study before any adjustments to pump settings.	Device: CGM and Insulin Pump; Dexcom G4 Platinum CGM with Share AP Receiver Roche Accu-Chek insulin pump
Experimental: Closed-Loop Control System with Zone MPC and HMS; The artificial pancreas system will be allowed to employ its Model Predictive Control algorithm to make decisions about insulin delivery based on measured glucose levels. The Health Monitoring System algorithm uses the same CGM data as the MPC control algorithm but utilizes a separate algorithm for trending and predictions of future glucose values. Using a redundant and independent algorithm is an important safety feature of the overall AP device.	Device: Closed-Loop Control System; The devices that will be used in the Closed-Loop Control System include the following components: DiAs - a smart-phone medical platform; Dexcom Dexcom G4 Platinum connected to DiAs via Bluetooth CGM receiver; Roche Accu-Chek insulin pump connected to DiAs via wireless Bluetooth; Remote Monitoring Server connected to DiAs via 3G or local Wi-Fi network, and Zone-MPC and HMS algorithms running on DiAs (MPC and HMS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and efficacy of the system, as assessed by the composite outcome of time in range for glucose levels of 70-180 mg/dL and time < 70 mg/dL.	The primary endpoint for this pilot study will be to determine the safety and efficacy of the system, as assessed by the composite outcome of time in range for glucose levels of 70-180 mg/dL and time < 70 mg/dL, comparing between sensor-augmented pump use (open loop care) (week 1) to closed-loop care (final week), so as to determine the feasibility of eventual long-term use of the system.	1 Week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time in range for glucose 80-140 mg/dL	Time in range for glucose 80-140 mg/dL at all times unless described otherwise.	1 Week
Time in range for glucose during the nocturnal period	Time in range for glucose 70-180 mg/dL during the nocturnal period.	1 week
Time in Range Postprandial	Time in range for glucose 70-180 mg/dL postprandial, for 5 hours following all meals	1 Week
Markers of hypo- and hyperglycemia	Markers of hypo- and hyperglycemia.	1 Week
Insulin Doses Given	Change in insulin doses given between the open and closed-loop phases of the study.	1 Week
Treatments for hypoglycemia	Treatments for hypoglycemia between the open and closed-loop phases of the study.	1 week
Number of alerts given by the HMS to prevent hypoglycemia	Number of alerts given by the HMS to prevent hypoglycemia during closed-Loop control.	2 Weeks
Outside interventions needed	Outside interventions needed to aid with treatment during closed-Loop control.	2 Weeks
Failure analysis of the devices/connectivity issues that may occur.	Failure analysis of the devices/connectivity issues that may occur during closed-Loop control.	2 Weeks

Collaborators and Investigators

• Sponsor: Sansum Diabetes Research Institute
• Collaborators: Mayo Clinic; University of Padova; University of Virginia; University of California, Santa Barbara
• Investigators: Principal Investigator: Francis J Doyle III, PhD, University of California, Santa Barbara/William Sansum Diabetes Center; Principal Investigator: Eyal Dassau, PhD, University of California, Santa Barbara/William Sansum Diabetes Center; Principal Investigator: Ananda Basu, MD, Mayo Clinic, Rochester, MN; Principal Investigator: Yogish Kudva, MD, Mayo Clinic, Rochester, MN; Principal Investigator: Boris Kovatchev, PhD, University of Virginia; Principal Investigator: Stephen Patek, PhD, University of Virginia

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): October 1, 2015
• Study Completion (Actual): October 1, 2015

Study Registration Dates

• First Submitted: May 28, 2015
• First Submitted That Met QC Criteria: June 3, 2015
• First Posted (Estimate): June 4, 2015

Study Record Updates

• Last Update Posted (Estimate): April 11, 2016
• Last Update Submitted That Met QC Criteria: April 7, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: Immune System Diseases; Diabetes Mellitus; Autoimmune Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Artificial Pancreas; Diabetes Mellitus, Type 1
• 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: 99796-JPIN