Outpatient Automated Blood Glucose Control With a Bi-hormonal Bionic Endocrine Pancreas

Study Overview
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Brief Summary
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This study will test the hypothesis that a wearable automated bionic pancreas system that automatically delivers both insulin and glucagon can improved glycemic control vs. usual in the outpatient environment.

Detailed Description
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The study population will be volunteers with type 1 diabetes who are 21 years of age or older. The setting will be an outpatient environment in a three square-mile area on the Boston Peninsula (see Appendix A). Volunteers will stay in a hotel adjacent to the MGH campus at night and will have free activity during the day within the specified geographic area. They will determine the timing and nature of their meals from local restaurants, with food brought from home, or food kept in their hotel room, which will have a small refrigerator. They will have the opportunity to exercise as they wish in their choice of two gyms. There will be minimal scheduling constraints, limited only by an 11:00 PM curfew and morning departure time from the hotel of no earlier than 7:00 AM. They will be able to work if they wish as long as that can be done within the geographical constraints (e.g. if they work in the downtown Boston area or can work from home or have meetings at a conference room in the hotel or at a restaurant). During the entire experiment they will be closely monitored by study staff (RN, NP, or MD) around the clock. They will remain within direct line of sight and no more than a short distance away from study staff during the daytime for safety. During the night they will be continuously monitored via BG telemetry from a nearby hotel room and study staff will be able to enter their rooms quickly, should that become necessary. During the night, when volunteers will remain in their rooms, one study staff member will monitor up to two volunteers at a time. Capillary BG will be tested every two hours during the day using a highly accurate, laboratory equivalent meter (HemoCue, selected for maximum data integrity) and venous BG will be tested every 30 minutes overnight using an autosampling device (GlucoScout). Continuous glucose monitoring (Dexcom G4) will be done throughout the study period. Photos and menu information, if available, will be documented for each meal and snack by the escort and estimates of carbohydrate intake will be estimated later from this information by a nutritionist. The type and level of activity being performed by the volunteers (e.g. lying, sitting, standing, walking, running) will be documented in 15 minute intervals by the study staff escort. Additional data will be collected using an accelerometer. During exercise, the type and duration of exercise, and, depending on the kind of activity, the heart rate (recorded using a Polar heart rate monitor) will be documented every 15 minutes and point-of-care blood glucose will be documented every 30 minutes.

Official Title
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The Beacon Hill Study: Feasibility of Outpatient Automated Blood Glucose Control With a Bi-hormonal Bionic Endocrine Pancreas

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Bi-homonal Bionic Pancreas
* Other: Usual care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 21 years or older with type 1 diabetes for at least one year Stimulated C-peptide < 0.1 nmol/L at 90 minutes after liquid mixed meal by the DCCT protocol Diabetes managed using an insulin infusion pump and rapid- or very-rapid-acting insulins including insulin aspart (NovoLog), insulin lispro (Humalog), and insulin glulisine (Apidra) for at least three months prior to enrollment Otherwise healthy (mild chronic disease such as asthma, hypertension, and depression will be allowed if well controlled) Exclusion Criteria: Unable to provide informed consent Unable to comply with study procedures Total daily dose (TDD) of insulin that is > 1.5 U/kg Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception. Hypoglycemia unawareness (self-reported lack of hypoglycemia symptoms when BG is < 50 mg/dl) End stage renal disease on dialysis (hemodialysis or peritoneal dialysis). Any known history of coronary artery disease (CAD) Abnormal EKG suggestive of coronary artery disease or increased risk of malignant arrhythmia Congestive heart failure (established history of CHF, paroxysmal nocturnal dyspnea, or orthopnea). History of TIA or stroke. History of pheochromocytoma. Fractionated metanephrines will be tested in patients with history increasing the risk for a catecholamine secreting tumor Untreated or inadequately treated mental illness Current alcohol abuse or substance abuse Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference. Use non-insulin, injectable anti-diabetic medications or oral anti-diabetic medications History of adverse reaction to glucagon (including allergy) besides nausea and vomiting Unwilling or unable to completely avoid acetaminophen ALT > 3-fold upper limit of normal Albumin < 3 g/dl Body mass index less than18 or greater than 35

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bi-homonal Bionic Pancreas<br>Closed-loop blood glucose control with a bi-hormonal bionic endocrine pancreas designed by Edward Damiano and Firas El-Khatib of Boston University. The device will deliver insulin lispro (Humalog) and glucagon based on blood glucose levels estimated by a continuous glucose monitoring device (Dexcom G4 Platinum) and a proprietary dosing algorithm. Blood glucose control will be automated for 5 days during which volunteers will sleep in a hotel and roam freely in downtown Boston during the day. There will be no restrictions on diet or exercise. | Device: Bi-homonal Bionic Pancreas<br>* A computer algorithm will automatically deliver insulin lispro and glucagon based on the signal from a minimally invasive continuous glucose monitor.<br>* Other names: Boston University Bionic Pancreas;|
| Active Comparator: Usual Care<br>Usual care for 5 days (insulin pump therapy according to usual practice), volunteers will sleep at home and maintain their usual schedule during the day, there will be no restrictions on diet or exercise, they will wear a blinded CGM | Other: Usual care<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Blood Glucose (Co-primary Outcome) | Average blood glucose during the closed-loop control period as determined from HemoCue capillary measurements (daytime+nightime) and GlucoScout venous measurements (nighttime). | 5 days of closed-loop control | 
| Percentage of Time Blood Glucose Values Less Than 70 mg/dl (Co-primary Outcome) | Percentage of time blood glucose values during the closed-loop control period less than 70 mg/dl determined from HemoCue capillary measurements (daytime) and GlucoScout venous measurements (nighttime) during day 1-5. During usual care (open loop), blood sugars were not checked through GlucoScout or HemoCue (as per usual care fashion) and so were not compared to bionic pancreas (closed loop) arm | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average BG During the Closed-loop Control Period as Determined From All HemoCue Measurements Taken During the Daytime and All Scheduled GlucoScout Measurements During the Nighttime. | During usual care (open loop), blood sugars were not checked through GlucoScout or HemoCue (as per usual care fashion) and so were not compared to bionic pancreas (closed loop) arm | 5 days | 
| Percentage of the Subset of BG Values Less Than 70 mg/dl as Determined From All All HemoCue Measurements Taken During the Daytime and Scheduled GlucoScout Measurements Taken During the Nighttime. |  | 5 days | 
| Difference in the Average BG Between the Closed-loop Control Period and the Usual Care Period. |  | 5 days | 
| Difference in the Percentage of the Above Subset of BG Values Between the Closed-loop Control and Usual Care Periods Less Than 70 mg/dl. |  | 5 days | 
| Percentage of Subjects With Mean BG < 154 mg/dl. | This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm. | 5 days | 
| Difference in the Percentage of Subjects With Mean BG < 154 mg/dl During the Closed-loop Period vs. the Usual Care Period. |  | 5 days | 
| Number of Hypoglycemic Events as Determined From GlucoScout and HemoCue Measurements. |  | 5 days | 
| Nadir BG During Exercise. |  | 5 days | 
| Correlation Between Exercise Intensity and Likelihood of a Hypoglycemic Event |  | 5 days | 
| Average BG During the Closed-loop Control Period as Determined From All GlucoScout Measurements Taken During the Nighttime Monitoring. | This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm. | 5 days | 
| Fraction of Time Spent Within Each of the Following Glucose Ranges as Determined From All GlucoScout and HemoCue Measurements. | Measurements adjusted for the frequency of measurement (i.e. modeled so that more frequent measurements at the time of hypoglycemia and exercise will not skew the mean): < 70 mg/dl,70-120 mg/dl,70-180 mg/dl, >180 mg/dl, >250 mg/dl | 5 Days | 
| Difference of Outcome Measures on Days 1-2 vs. on Remaining Days (Days 3-5) During the Closed-loop Period. |  | 5 Days | 
| Mean BG During Exercise. |  | 5 days | 
| Number of Hypoglycemic Episodes During Exercise. |  | 5 days | 
| Difference of Outcome Measures on Day 1 vs. Remaining Days (Days 2-5) During the Closed-loop Period. |  | 5 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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bionic pancreas, artificial pancreas, insulin, glucagon, continuous glucose monitoring, CGM, outpatient, insulin pump