Closed-Loop Glucagon Administration For Hypoglycemia Treatment

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 glucagon only can prevent or treat hypoglycemia vs. usual care for people with type 1 diabetes > 21 years old.

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

Conditions
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Type 1 Diabetes

Intervention / Treatment
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* Device: Glucagon-only Bionic Pancreas


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. 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.

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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Accepts Healthy Volunteers

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Glucagon-only Bionic Pancreas (active)<br>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<br>* A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.<br>* Other names: Boston University Bionic Pancreas;|
| Placebo Comparator: Glucagon-only Bionic Pancreas (placebo)<br>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<br>* A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.<br>* Other names: Boston University Bionic Pancreas;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | 

 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, glucagon pump