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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01762059

Enrollment

Registered

2013-01-07

Start date

2013-01-31

Completion date

2014-06-30

Last updated

2017-07-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Type 1 Diabetes

Keywords

bionic pancreas, artificial pancreas, insulin, glucagon, continuous glucose monitoring, CGM, outpatient, insulin pump

Brief summary

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

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.

Interventions

DEVICEBi-homonal Bionic Pancreas

A computer algorithm will automatically deliver insulin lispro and glucagon based on the signal from a minimally invasive continuous glucose monitor.

OTHERUsual care

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

21 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Average Blood Glucose (Co-primary Outcome)	5 days of closed-loop control	Average blood glucose during the closed-loop control period as determined from HemoCue capillary measurements (daytime+nightime) and GlucoScout venous measurements (nighttime).
Percentage of Time Blood Glucose Values Less Than 70 mg/dl (Co-primary Outcome)	5 days	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

Secondary

Measure	Time frame	Description
Difference in the Percentage of Subjects With Mean BG < 154 mg/dl During the Closed-loop Period vs. the Usual Care Period.	5 days	—
Fraction of Time Spent Within Each of the Following Glucose Ranges as Determined From All GlucoScout and HemoCue Measurements.	5 Days	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
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	—
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.	5 days	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
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.	5 days	This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.
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.	5 days	This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.

Other

Measure	Time frame
Mean Blood Sugar as Measured by Continuous Glucose Monitor (CGM) Readings	Days 2-5
Fraction of Time Spent Within Each of the Following Glucose Ranges: < 70 mg/dl,70-120 mg/dl,70-180 mg/dl,>180 mg/dl,>250 mg/dl	Days 2-5
Difference in the Percentage of Subjects With Mean CGMG <154mg/dl During the Closed-loop Period vs. the Usual Care Period	5 days
Percentage of Subjects With Mean CGMG < 154mg/dl	5 days

Countries

United States

Participant flow

Participants by arm

Arm	Count
All Participants	20
Total	20

Baseline characteristics

Characteristic	All Participants
Age, Continuous	40 years STANDARD_DEVIATION 16
Sex: Female, Male Female	12 Participants
Sex: Female, Male Male	8 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	— / —
other Total, other adverse events	8 / 20
serious Total, serious adverse events	0 / 20

Outcome results

Primary

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).

Time frame: 5 days of closed-loop control

Population: This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.

Arm	Measure	Value (MEAN)	Dispersion
Bionic Pancreas	Average Blood Glucose (Co-primary Outcome)	138 mg/dL	Standard Deviation 14

Primary

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

Time frame: 5 days

Population: This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.

Arm	Measure	Value (MEAN)	Dispersion
Bionic Pancreas	Percentage of Time Blood Glucose Values Less Than 70 mg/dl (Co-primary Outcome)	4.8 percentage of time	Standard Deviation 5.2

Secondary

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.

Time frame: 5 days

Population: This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.

Arm	Measure	Value (MEAN)	Dispersion
Bionic Pancreas	Average BG During the Closed-loop Control Period as Determined From All GlucoScout Measurements Taken During the Nighttime Monitoring.	125 mg/dl	Standard Deviation 19

Secondary

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

Time frame: 5 days

Population: This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.

Arm	Measure	Value (MEAN)	Dispersion
Bionic Pancreas	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.	138 mg/dl	Standard Deviation 14

Secondary