Closed-Loop Glucagon Administration For Hypoglycemia Treatment

Closed-Loop Glucagon Administration for the Automated Prevention and Treatment of Hypoglycemia

This study will test the hypothesis that a wearable automated bionic pancreas system that automatically delivers glucagon only can prevent or treat hypoglycemia vs. usual care for people with type 1 diabetes > 21 years old.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes
• Intervention / Treatment: Device: Glucagon-only Bionic Pancreas

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age 21 years or older with type 1 diabetes for at least one year.
• Otherwise healthy (mild chronic disease such as asthma, hypertension, and depression will be allowed if well controlled).
• Self-reported frequency of documented hypoglycemia (BG < 60 mg/dl) of at least 2 times per week
• Partial hypoglycemic unawareness (inconsistent symptoms with BG < 50 mg/dl) or hypoglycemic unawareness (minimal or no symptoms with BG < 50 mg/dl)

Exclusion Criteria:

• Unable to provide informed consent.
• Unable to comply with study procedures.
• Current participation in another diabetes-related clinical trial other than one that is primarily observational in nature.
• Pregnancy (positive urine HCG), breast feeding, plan to become pregnant in the immediate future, or sexually active without use of contraception
• History of cystic fibrosis, pancreatitis, or other pancreatic disease other than type 1 diabetes
• End stage renal disease on dialysis (hemodialysis or peritoneal dialysis).
• Any known liver or biliary disease including cirrhosis, alcoholic liver disease, non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, any form of viral hepatitis.
• Congestive heart failure (established history of CHF, paroxysmal nocturnal dyspnea, or orthopnea).
• Acute illness or exacerbation of chronic illness at the time of the study.
• Seizure disorder or history of hypoglycemic seizure in the last 1 year
• 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 (indicators would include symptoms such as psychosis, hallucinations, mania, and any psychiatric hospitalization in the last year).
• Current alcohol abuse (intake averaging > 3 drinks daily in last 30 days) or substance abuse (any use within the last 6 months of controlled substances without a prescription).
• Electrically powered implants (e.g. cochlear implants, neurostimulators) that might be susceptible to RF interference.
• History of adverse reaction to glucagon (including allergy) besides nausea and vomiting.
• Unwilling or unable to completely avoid acetaminophen during the study period.
• Any factors that, in the opinion of the principal investigator, would interfere with the safe completion of the study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Glucagon-only Bionic Pancreas (active); Glucagon-only Bionic Pancreas will deliver glucagon during 7 of the 14 days. The order of the glucagon days will be randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Device: Glucagon-only Bionic Pancreas; A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.; Other Names: Boston University Bionic Pancreas
Placebo Comparator: Glucagon-only Bionic Pancreas (placebo); Glucagon-only Bionic Pancreas will deliver placebo during 7 of the 14 days. The order of the placebo days will be randomized in blocks of 2, with no more than 2 days in a row of placebo.	Device: Glucagon-only Bionic Pancreas; A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.; Other Names: Boston University Bionic Pancreas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Continuous Glucose Monitor (CGM) Glucose Total Area Over the Curve and Less Than 60 mg/dl	From t=0 to study stop after 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime		2 weeks
Number of Hypoglycemic Episodes With CGMG < 50 mg/dl		From t=0 to study stop after 2 weeks
Number of Hypoglycemic Episodes With CGMG < 60 mg/dl		from t=0 to study stop after 2 weeks
Number of Hypoglycemic Episodes With CGMG < 70 mg/dl		from t=0 to study stop after 2 weeks
Fraction of Time Spent Within Each of the Following Glucose Ranges as Determined From All CGMG Measurements: < 70 mg/dl,70-120 mg/dl,70-180 mg/dl, >180 mg/dl, >250 mg/dl		from t=0 to stud stop after 2 weeks
Count of Subjects With Mean CGMG < 154mg/dl		from t=0 to study stop after 2 weeks
Mean CGMG During Exercise	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.	2 weeks
Mean Absolute Relative Deviation (MARD) vs. Subset of BG Measurements Before Meals and at Bedtime	Blood sugar measurements were not specified as before meals and before bed during the study, so we are unable to calculate and report this outcome.	2 weeks
Mean Absolute Relative Deviation (MARD) Between Capillary Blood Glucose and CGM Glucose Values	Paired values between the blood glucose measurements and CGM glucose measurements were compared, and the percent difference was recorded. The mean of the absolute value of all the differences is reported here, and reflects the accuracy of the CGM glucose measurements relative to the capillary blood glucose measurements.	from t=0 to study stop after 2 weeks
Number of Hypoglycemic Events (< 60 mg/dl) as Determined From BG Measurements		from t=0 to study stop after 2 weeks
Average BG as Determined From the Measurements Taken Before Meals and Before Bedtime	Blood sugar measurements were not specified as before meals and before bed during the study, so we are unable to calculate and report this outcome.	2 weeks
Percentage of the BG Values Taken Before Meals and Before Bedimte Less Than 70 mg/dl	Blood sugar measurements were not specified as before meals and before bed during the study, so we are unable to calculate and report this outcome.	2 weeks
Number of All BG Values Less Than 70 mg/dl		from t=0 to study stop after 2 weeks
Number of Study Days With Mean BG < 154 mg/dl		2 weeks
Fraction Measurements Within Each of the Following Glucose Ranges as Determined From HemoCue Measurements Taken Before Meals and Before Bed: < 70 mg/dl,70-120 mg/dl,70-180 mg/dl,>180 mg/dl,>250 mg/dl	Blood sugar measurements were not specified as before meals and before bed during the study, so we are unable to calculate and report this outcome.	2 weeks
Mean BG During Exercise	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.	2 weeks
• Fraction of BG Values < 70 During Exercise Fraction of BG Values < 70 During Exercise	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.	2 weeks
Number of Carbohydrate Interventions for Hypoglycemia		from t=0 to study stop after 2 weeks
Total Number of Grams of Carbohydrate Taken for Hypoglycemia		from t=0 to study stop after 2 weeks
Insulin Total Daily Dose		from t=0 to study stop after 2 weeks
• Number of Carbohydrate Interventions for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated	2 weeks
Total Number of Grams of Carbohydrate Taken for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated	2 weeks
Number of Carbohydrate Interventions for Hypoglycemia Overnight (11:00 PM - 7:00 AM)	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated	2 weeks
Total Number of Grams of Carbohydrate Taken for Hypoglycemia Overnight (11:00 PM - 7:00 AM)	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated	2 weeks
Total Glucagon Dosing (mcg/kg/24 Hours)		from t=0 to study stop after 2 weeks
Episodes of Nausea Per Day on Glucagon vs Placebo		from t=0 to study stop after 2 weeks

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Boston University

Publications and helpful links

Helpful Links

• Information about this and related studies

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): June 1, 2015
• Study Completion (Actual): April 1, 2017

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: July 1, 2014
• First Posted (Estimate): July 3, 2014

Study Record Updates

• Last Update Posted (Actual): January 10, 2019
• Last Update Submitted That Met QC Criteria: December 19, 2018
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: glucagon; insulin pump; artificial pancreas; insulin; outpatient; bionic pancreas; continuous glucose monitoring (CGM); glucagon pump
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hypoglycemia; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon; Pancrelipase; Pancreatin
• Other Study ID Numbers: 2013P001663/MGH

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No