Trial Outcomes & Findings for Closed-Loop Glucagon Administration For Hypoglycemia Treatment (NCT NCT02181127)

NCT ID: NCT02181127

Last Updated: 2019-01-10

Results Overview

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 31 participants
• Primary outcome timeframe: From t=0 to study stop after 2 weeks
• Results posted on: 2019-01-10

Participant Flow

31 participants were enrolled in the trial, but only 22 participants actually participated. 4 subjects were not eligible to participate. The remaining 5 subjects that did not participate were considered "back up" or "benched" subjects who were eligible and willing to participate, but were not required to meet our desired total cohort.

Participant milestones

Measure	Glucagon-only Bionic Pancreas Subjects will use the device every day and will fill the reservoir daily with glucagon or placebo (randomized, double blinded allocation for each day). Glucagon-only Bionic Pancreas: A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.
Overall Study STARTED	22
Overall Study COMPLETED	22
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Closed-Loop Glucagon Administration For Hypoglycemia Treatment

Baseline characteristics by cohort

Measure	Glucagon-only Bionic Pancreas n=22 Participants Subjects will use the device every day and will fill the reservoir daily with glucagon or placebo (randomized, double blinded allocation for each day). Glucagon-only Bionic Pancreas: A computer algorithm will automatically deliver glucagon based on the signal from a minimally invasive continuous glucose monitor.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants
Age, Categorical >=65 years	2 Participants n=5 Participants
Age, Continuous	41.9 years STANDARD_DEVIATION 15.2 • n=5 Participants
Sex: Female, Male Female	16 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants

PRIMARY outcome

Timeframe: From t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Continuous Glucose Monitor (CGM) Glucose Total Area Over the Curve and Less Than 60 mg/dl	1015 mg/dl/min Standard Deviation 883.24	4375.68 mg/dl/min Standard Deviation 3058.77

SECONDARY outcome

Timeframe: 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime Glucagon - daytime	3.92 percentage of time Standard Deviation 2.42	—
Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime Glucagon - overnight	1.50 percentage of time Standard Deviation 2.18	—
Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime Placebo - daytime	7.94 percentage of time Standard Deviation 4.62	—
Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime Placebo - overnight	10.25 percentage of time Standard Deviation 7.15	—

SECONDARY outcome

Timeframe: From t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Hypoglycemic Episodes With CGMG < 50 mg/dl	1.73 number of episodes Standard Deviation 1.39	5.0 number of episodes Standard Deviation 3.07

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Hypoglycemic Episodes With CGMG < 60 mg/dl	4.14 number of episodes Standard Deviation 2.23	8.86 number of episodes Standard Deviation 4.57

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Hypoglycemic Episodes With CGMG < 70 mg/dl	8.95 number of episodes Standard Deviation 5.55	12.68 number of episodes Standard Deviation 5.54

SECONDARY outcome

Timeframe: from t=0 to stud stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
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 CGMG > 180 mg/dl	27.98 percentage of time Standard Deviation 16.44	29.38 percentage of time Standard Deviation 15.74
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 CGMG > 250 mg/dl	9.05 percentage of time Standard Deviation 8.05	9.83 percentage of time Standard Deviation 8.14
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 CGMG < 70 mg/dl	3.11 percentage of time Standard Deviation 2.02	8.73 percentage of time Standard Deviation 5.10
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 CGMG 70-120 mg/dl	33.32 percentage of time Standard Deviation 15.85	30.53 percentage of time Standard Deviation 14.74
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 CGMG 70-180 mg/dl	68.91 percentage of time Standard Deviation 15.39	61.89 percentage of time Standard Deviation 13.79

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Count of Subjects With Mean CGMG < 154mg/dl	13 Participants	11 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Population: This analysis is not broken down according to randomization, because it is intended to give context to the other CGM reported outcomes by reflecting the accuracy of the CGM.

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.

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Mean Absolute Relative Deviation (MARD) Between Capillary Blood Glucose and CGM Glucose Values	15.20 percent difference Standard Deviation 14.56	—

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Hypoglycemic Events (< 60 mg/dl) as Determined From BG Measurements	0.73 number of events Standard Deviation 0.98	2.59 number of events Standard Deviation 2.59

SECONDARY outcome

Timeframe: 2 weeks

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of All BG Values Less Than 70 mg/dl	1.45 number of values Standard Deviation 1.99	4.23 number of values Standard Deviation 3.90

SECONDARY outcome

Timeframe: 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Study Days With Mean BG < 154 mg/dl	4.4 number of days Standard Deviation 2.2	4.2 number of days Standard Deviation 2.2

SECONDARY outcome

Timeframe: 2 weeks

Population: 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.

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.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Number of Carbohydrate Interventions for Hypoglycemia	1.25 number of interventions per day Standard Deviation 0.48	1.89 number of interventions per day Standard Deviation 0.83

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Total Number of Grams of Carbohydrate Taken for Hypoglycemia	23.90 grams per day Standard Deviation 9.52	36.29 grams per day Standard Deviation 22.95

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Insulin Total Daily Dose	38.7 units per day Standard Deviation 12.6	37.0 units per day Standard Deviation 12.0

SECONDARY outcome

Timeframe: 2 weeks

Population: Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 2 weeks

Population: Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Total Glucagon Dosing (mcg/kg/24 Hours)	6.84 mcg/kg/day Standard Deviation 2.90	9.8 mcg/kg/day Standard Deviation 3.6

SECONDARY outcome

Timeframe: from t=0 to study stop after 2 weeks

Outcome measures

Measure	Glucagon-only Bionic Pancreas n=22 Participants Glucagon-only Bionic Pancreas delivered glucagon during 7 of the 14 days. The order of the glucagon days was randomized in blocks of 2, with no more than 2 days in a row of glucagon.	Placebo n=22 Participants Glucagon-only Bionic Pancreas delivered placebo during 7 of the 14 days. The order of the placebo days was randomized in blocks of 2, with no more than 2 days in a row of placebo.
Episodes of Nausea Per Day on Glucagon vs Placebo	1.1 episodes of nausea per day Standard Deviation 1.6	0.4 episodes of nausea per day Standard Deviation .07

Adverse Events

Glucagon-only Bionic Pancreas

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Steven J Russell

Massachusetts General Hospital

Phone: 617-726-1848

Email: sjrussell@partners.org

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place