Clinical trial NCT02181127: Closed-Loop Glucagon Administration For Hypoglycemia Treatment
Official title: Closed-Loop Glucagon Administration for the Automated Prevention and Treatment of Hypoglycemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes
Keywords: bionic pancreas
artificial pancreas
insulin
glucagon
continuous glucose monitoring (CGM)
outpatient
insulin pump
glucagon pump
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston University
First posted: 2014-07-03
Enrollment: 31
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Continuous Glucose Monitor (CGM) Glucose Total Area Over the Curve and Less Than 60 mg/dl
timeFrame: From t=0 to study stop after 2 weeks
Secondary outcomes:
measure: Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime
timeFrame: 2 weeks
measure: Number of Hypoglycemic Episodes With CGMG < 50 mg/dl
timeFrame: From t=0 to study stop after 2 weeks
measure: Number of Hypoglycemic Episodes With CGMG < 60 mg/dl
timeFrame: from t=0 to study stop after 2 weeks
measure: Number of Hypoglycemic Episodes With CGMG < 70 mg/dl
timeFrame: from t=0 to study stop after 2 weeks
measure: 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
timeFrame: from t=0 to stud stop after 2 weeks
measure: Count of Subjects With Mean CGMG < 154mg/dl
timeFrame: from t=0 to study stop after 2 weeks
measure: Mean CGMG During Exercise
timeFrame: 2 weeks
measure: Mean Absolute Relative Deviation (MARD) vs. Subset of BG Measurements Before Meals and at Bedtime
timeFrame: 2 weeks
measure: Mean Absolute Relative Deviation (MARD) Between Capillary Blood Glucose and CGM Glucose Values
timeFrame: from t=0 to study stop after 2 weeks
measure: Number of Hypoglycemic Events (< 60 mg/dl) as Determined From BG Measurements
timeFrame: from t=0 to study stop after 2 weeks
measure: Average BG as Determined From the Measurements Taken Before Meals and Before Bedtime
timeFrame: 2 weeks
measure: Percentage of the BG Values Taken Before Meals and Before Bedimte Less Than 70 mg/dl
timeFrame: 2 weeks
measure: Number of All BG Values Less Than 70 mg/dl
timeFrame: from t=0 to study stop after 2 weeks
measure: Number of Study Days With Mean BG < 154 mg/dl
timeFrame: 2 weeks
measure: 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
timeFrame: 2 weeks
measure: Mean BG During Exercise
timeFrame: 2 weeks
measure: • Fraction of BG Values < 70 During Exercise Fraction of BG Values < 70 During Exercise
timeFrame: 2 weeks
measure: Number of Carbohydrate Interventions for Hypoglycemia
timeFrame: from t=0 to study stop after 2 weeks
measure: Total Number of Grams of Carbohydrate Taken for Hypoglycemia
timeFrame: from t=0 to study stop after 2 weeks
measure: Insulin Total Daily Dose
timeFrame: from t=0 to study stop after 2 weeks
measure: • Number of Carbohydrate Interventions for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)
timeFrame: 2 weeks
measure: Total Number of Grams of Carbohydrate Taken for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)
timeFrame: 2 weeks
measure: Number of Carbohydrate Interventions for Hypoglycemia Overnight (11:00 PM - 7:00 AM)
timeFrame: 2 weeks
measure: Total Number of Grams of Carbohydrate Taken for Hypoglycemia Overnight (11:00 PM - 7:00 AM)
timeFrame: 2 weeks
measure: Total Glucagon Dosing (mcg/kg/24 Hours)
timeFrame: from t=0 to study stop after 2 weeks
measure: Episodes of Nausea Per Day on Glucagon vs Placebo
timeFrame: from t=0 to study stop after 2 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Steven J Russell, MD PhD
role: PRINCIPAL_INVESTIGATOR
References: