Clinical trial NCT02705053: At Home Study of a Zone-Model Predictive Control (MPC) Controller and a Health Monitoring System (HMS) With the Diabetes Assistant (DiAs) System and Run-to-Run Adaptation
Official title: At Home Study of a Zone-Model Predictive Control (MPC) Controller and a Health Monitoring System (HMS) With the Diabetes Assistant (DiAs) System and Run-to-Run Adaptation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Keywords: Diabetes Mellitus, Type 1
Artificial Pancreas
Autoimmune Diseases
Diabetes Mellitus
Hyperglycemia
Hypoglycemia
Lead sponsor: Sansum Diabetes Research Institute
Sponsor class: OTHER
Collaborators: name: Harvard University
name: University of California, Santa Barbara
name: Mayo Clinic
name: University of Virginia
name: University of Padova
First posted: 2016-03-10
Enrollment: 32
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This clinical trial is a study to assess the performance of an automated glucose control system (Artificial Pancreas, AP) device in home settings for subjects with type 1 diabetes. Specifically, the investigators will test zone model predictive control AP that will be enhanced by run-to-run optimizations of basal rates (BR) and insulin to carbohydrate ratios (CR).

Detailed description: This clinical trial is a study to assess the performance of an automated glucose control system (Artificial Pancreas, AP) device in home settings for subjects with type 1 diabetes. Specifically, the investigators will test zone model predictive control AP that will be enhanced by run-to-run optimizations of basal rates (BR) and insulin to carbohydrate ratios (CR). This protocol builds on the investigators previously validated Zone-MPC and Health Monitoring System (HMS) algorithms (ClinicalTrials.gov: NCT01929798) integrated into the Diabetes Assistant (DiAs) system (ClinicalTrials.gov: NCT02463682). The same AP system used in NCT02463682 will now be used with algorithmic adjustment of CR's prior to closed-loop initiation, and continued BR and CR algorithmic optimization during closed-loop use for a longer duration.

The system will be evaluated on up to 12 subjects per site (n=36 subjects) for 15 weeks at 3 different sites (William Sansum Diabetes Center, University of Virginia, and Mayo Clinic, Rochester, MN).

Eligibility criteria: 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 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:

  1. Inpatient psychiatric treatment in the past 6 months for either the subject or the subject's primary care giver (i.e., parent or guardian)
  2. Presence of a known adrenal disorder
  3. 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
  4. 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
  5. Active gastroparesis
  6. 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
  7. 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
  8. Abuse of alcohol or recreational drugs
  9. 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:

  1. Acetaminophen
  2. Beta blockers
  3. Oral or injectable glucocorticoids
  4. Any other medication that the investigator believes is a contraindication to the subject's participation

Primary outcomes:
measure: Change in Hemoglobin A1c (HbA1c) (%) from baseline (week 2) to end of week 15 (end of study), with A1c measured at weeks 7 and 11 as well for repeated measures.
timeFrame: 13 Weeks
Secondary outcomes:
measure: Time within the target range for glucose 70-180 mg/dl overall
timeFrame: 1 week
measure: Time within the tight target range for glucose 80-140 mg/dl overnight
timeFrame: 1 week
measure: Time within the target range for glucose 70-150 mg/dl postprandial within 5 hours following meals
timeFrame: 1 week
measure: Markers of hypo- and hyperglycemia
timeFrame: 1 week
measure: Insulin Doses Given
timeFrame: 1 week
measure: Treatments for hypoglycemia
timeFrame: 1 week
measure: Number of alerts given by the HMS to prevent hypoglycemia
timeFrame: 12 weeks
measure: Outside interventions needed.
timeFrame: 12 weeks
measure: Failure analysis of the devices/connectivity issues that may occur (# disconnects and device restarts).
timeFrame: 12 weeks
measure: Time with glucose ≤ 70 mg/dL, overall
timeFrame: 1 week
Other outcomes:
Locations:
city: Santa Barbara
country: United States
facility: William Sansum Diabetes Center
state: California
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Harvard University
name: Francis J Doyle III, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Harvard University
name: Eyal Dassau, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sansum Diabetes Research Institute
name: Jordan E Pinsker, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic, Rochester, MN
name: Ananda Basu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic, Rochester, MN
name: Yogish Kudva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Boris Kovatchev, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Sue Brown, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Virginia
name: Stephen Patek, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Padova
name: Claudio Cobelli, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Dassau E, Pinsker JE, Kudva YC, Brown SA, Gondhalekar R, Dalla Man C, Patek S, Schiavon M, Dadlani V, Dasanayake I, Church MM, Carter RE, Bevier WC, Huyett LM, Hughes J, Anderson S, Lv D, Schertz E, Emory E, McCrady-Spitzer SK, Jean T, Bradley PK, Hinshaw L, Laguna Sanz AJ, Basu A, Kovatchev B, Cobelli C, Doyle FJ 3rd. Twelve-Week 24/7 Ambulatory Artificial Pancreas With Weekly Adaptation of Insulin Delivery Settings: Effect on Hemoglobin A1c and Hypoglycemia. Diabetes Care. 2017 Dec;40(12):1719-1726. doi: 10.2337/dc17-1188. Epub 2017 Oct 13.