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

• ClinicalTrials.gov Identifier: NCT01762059
• Recruitment Status: Completed
• First Posted: January 7, 2013
• Results First Posted: July 21, 2017
• Last Update Posted: July 21, 2017
• Sponsor: Massachusetts General Hospital
• Collaborator: Boston University
• Information provided by (Responsible Party): Steven J. Russell, MD, PhD, Massachusetts General Hospital

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Type 1 Diabetes	Device: Bi-homonal Bionic Pancreas; Other: Usual care	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Beacon Hill Study: Feasibility of Outpatient Automated Blood Glucose Control With a Bi-hormonal Bionic Endocrine Pancreas
• Study Start Date: January 2013
• Actual Primary Completion Date: October 2013
• Actual Study Completion Date: June 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Bi-homonal Bionic Pancreas; 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; A computer algorithm will automatically deliver insulin lispro and glucagon based on the signal from a minimally invasive continuous glucose monitor.; Other Name: Boston University Bionic Pancreas
Active Comparator: Usual Care; 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

Outcome Measures

Primary Outcome Measures :

1. Average Blood Glucose (Co-primary Outcome) [ Time Frame: 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).
2. Percentage of Time Blood Glucose Values Less Than 70 mg/dl (Co-primary Outcome) [ Time Frame: 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 Outcome Measures :

1. 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. [ Time Frame: 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
2. 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. [ Time Frame: 5 days ]
3. Difference in the Average BG Between the Closed-loop Control Period and the Usual Care Period. [ Time Frame: 5 days ]
4. 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. [ Time Frame: 5 days ]
5. Percentage of Subjects With Mean BG < 154 mg/dl. [ Time Frame: 5 days ]
   This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.
6. Difference in the Percentage of Subjects With Mean BG < 154 mg/dl During the Closed-loop Period vs. the Usual Care Period. [ Time Frame: 5 days ]
7. Number of Hypoglycemic Events as Determined From GlucoScout and HemoCue Measurements. [ Time Frame: 5 days ]
8. Nadir BG During Exercise. [ Time Frame: 5 days ]
9. Correlation Between Exercise Intensity and Likelihood of a Hypoglycemic Event [ Time Frame: 5 days ]
10. Average BG During the Closed-loop Control Period as Determined From All GlucoScout Measurements Taken During the Nighttime Monitoring. [ Time Frame: 5 days ]
    This outcome measure was only assessed for the closed loop control period, and was not assessed during the usual care arm.
11. Fraction of Time Spent Within Each of the Following Glucose Ranges as Determined From All GlucoScout and HemoCue Measurements. [ Time Frame: 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

12. Difference of Outcome Measures on Days 1-2 vs. on Remaining Days (Days 3-5) During the Closed-loop Period. [ Time Frame: 5 Days ]
13. Mean BG During Exercise. [ Time Frame: 5 days ]
14. Number of Hypoglycemic Episodes During Exercise. [ Time Frame: 5 days ]
15. Difference of Outcome Measures on Day 1 vs. Remaining Days (Days 2-5) During the Closed-loop Period. [ Time Frame: 5 Days ]

Other Outcome Measures:

1. Percentage of Subjects With Mean CGMG < 154mg/dl [ Time Frame: 5 days ]
2. Difference in the Percentage of Subjects With Mean CGMG <154mg/dl During the Closed-loop Period vs. the Usual Care Period [ Time Frame: 5 days ]
3. 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 [ Time Frame: Days 2-5 ]
4. Mean Blood Sugar as Measured by Continuous Glucose Monitor (CGM) Readings [ Time Frame: Days 2-5 ]

Eligibility Criteria

• Ages Eligible for Study: 21 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Boston University

Investigators

• Principal Investigator: Steven J Russell, MD PhD; Massachusetts General Hospital

More Information

Additional Information:

Information about this and related studies 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Russell SJ, El-Khatib FH, Sinha M, Magyar KL, McKeon K, Goergen LG, Balliro C, Hillard MA, Nathan DM, Damiano ER. Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med. 2014 Jul 24;371(4):313-325. doi: 10.1056/NEJMoa1314474. Epub 2014 Jun 15.

• Responsible Party: Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT01762059
• Other Study ID Numbers: 2012P002317
• First Posted: January 7, 2013
• Results First Posted: July 21, 2017
• Last Update Posted: July 21, 2017
• Last Verified: June 2017

Keywords provided by Steven J. Russell, MD, PhD, Massachusetts General Hospital:

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

Additional relevant MeSH terms:

Diabetes Mellitus, Type 1; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Pancrelipase; Pancreatin; Gastrointestinal Agents