Closed-Loop Glucagon Administration For Hypoglycemia Treatment

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT02181127
• Collaborator: Boston University (Other)
• Enrollment: 31
• Location: 1
• Arms: 2
• Duration (Months): 29
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes	Device: Glucagon-only Bionic Pancreas	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 31 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Closed-Loop Glucagon Administration for the Automated Prevention and Treatment of Hypoglycemia
• Study Start Date: Nov 1, 2014
• Actual Primary Completion Date: Jun 1, 2015
• Actual Study Completion Date: Apr 1, 2017

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. 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

1. Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime [2 weeks]

2. Number of Hypoglycemic Episodes With CGMG < 50 mg/dl [From t=0 to study stop after 2 weeks]

3. Number of Hypoglycemic Episodes With CGMG < 60 mg/dl [from t=0 to study stop after 2 weeks]

4. Number of Hypoglycemic Episodes With CGMG < 70 mg/dl [from t=0 to study stop after 2 weeks]

5. 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]

6. Count of Subjects With Mean CGMG < 154mg/dl [from t=0 to study stop after 2 weeks]

7. Mean CGMG During Exercise [2 weeks]

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

8. Mean Absolute Relative Deviation (MARD) vs. Subset of BG Measurements Before Meals and at Bedtime [2 weeks]

   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.

9. Mean Absolute Relative Deviation (MARD) Between Capillary Blood Glucose and CGM Glucose Values [from t=0 to study stop after 2 weeks]

   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.

10. Number of Hypoglycemic Events (< 60 mg/dl) as Determined From BG Measurements [from t=0 to study stop after 2 weeks]

11. Average BG as Determined From the Measurements Taken Before Meals and Before Bedtime [2 weeks]

    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.

12. Percentage of the BG Values Taken Before Meals and Before Bedimte Less Than 70 mg/dl [2 weeks]

    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.

13. Number of All BG Values Less Than 70 mg/dl [from t=0 to study stop after 2 weeks]

14. Number of Study Days With Mean BG < 154 mg/dl [2 weeks]

15. 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 [2 weeks]

    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.

16. Mean BG During Exercise [2 weeks]

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

17. • Fraction of BG Values < 70 During Exercise Fraction of BG Values < 70 During Exercise [2 weeks]

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

18. Number of Carbohydrate Interventions for Hypoglycemia [from t=0 to study stop after 2 weeks]

19. Total Number of Grams of Carbohydrate Taken for Hypoglycemia [from t=0 to study stop after 2 weeks]

20. Insulin Total Daily Dose [from t=0 to study stop after 2 weeks]

21. • Number of Carbohydrate Interventions for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM) [2 weeks]

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

22. Total Number of Grams of Carbohydrate Taken for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM) [2 weeks]

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

23. Number of Carbohydrate Interventions for Hypoglycemia Overnight (11:00 PM - 7:00 AM) [2 weeks]

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

24. Total Number of Grams of Carbohydrate Taken for Hypoglycemia Overnight (11:00 PM - 7:00 AM) [2 weeks]

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

25. Total Glucagon Dosing (mcg/kg/24 Hours) [from t=0 to study stop after 2 weeks]

26. Episodes of Nausea Per Day on Glucagon vs Placebo [from t=0 to study stop after 2 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Information about this and related studies

Publications

None provided.

• Responsible Party: Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT02181127
• Other Study ID Numbers: 2013P001663/MGH
• First Posted: Jul 3, 2014
• Last Update Posted: Jan 10, 2019
• Last Verified: Dec 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Steven J. Russell, MD, PhD, Assistant Professor of Medicine, Massachusetts General Hospital: bionic pancreas; artificial pancreas; insulin; glucagon; continuous glucose monitoring (CGM); outpatient; insulin pump; glucagon pump
• Additional relevant MeSH terms: Hypoglycemia; Glucagon; Pancrelipase; Pancreatin

Study Results

Participant Flow

Pre-assignment Detail	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.

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Period Title: Overall Study
STARTED	22
COMPLETED	22
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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 Participants	22
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 90.9%
>=65 years	2 9.1%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.9 (15.2)
Sex: Female, Male (Count of Participants)
Female	16 72.7%
Male	6 27.3%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [mg/dl/min]	1015 (883.24)	4375.68 (3058.77)

2. Secondary Outcome

Title	Percentage of Time CGM Glucose Less Than 70 mg/dl Overnight and During Daytime
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	22
Glucagon - daytime	3.92 (2.42)
Glucagon - overnight	1.50 (2.18)
Placebo - daytime	7.94 (4.62)
Placebo - overnight	10.25 (7.15)

3. Secondary Outcome

Title	Number of Hypoglycemic Episodes With CGMG < 50 mg/dl
Time Frame	From t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of episodes]	1.73 (1.39)	5.0 (3.07)

4. Secondary Outcome

Title	Number of Hypoglycemic Episodes With CGMG < 60 mg/dl
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of episodes]	4.14 (2.23)	8.86 (4.57)

5. Secondary Outcome

Title	Number of Hypoglycemic Episodes With CGMG < 70 mg/dl
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of episodes]	8.95 (5.55)	12.68 (5.54)

6. Secondary Outcome

Title	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
Time Frame	from t=0 to stud stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
CGMG < 70 mg/dl	3.11 (2.02)	8.73 (5.10)
CGMG 70-120 mg/dl	33.32 (15.85)	30.53 (14.74)
CGMG 70-180 mg/dl	68.91 (15.39)	61.89 (13.79)
CGMG > 180 mg/dl	27.98 (16.44)	29.38 (15.74)
CGMG > 250 mg/dl	9.05 (8.05)	9.83 (8.14)

7. Secondary Outcome

Title	Count of Subjects With Mean CGMG < 154mg/dl
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Count of Participants [Participants]	13 59.1%	11 NaN

8. Secondary Outcome

Title	Mean CGMG During Exercise
Description	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

9. Secondary Outcome

Title	Mean Absolute Relative Deviation (MARD) vs. Subset of BG Measurements Before Meals and at Bedtime
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

10. Secondary Outcome

Title	Mean Absolute Relative Deviation (MARD) Between Capillary Blood Glucose and CGM Glucose Values
Description	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.
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	All Participants
Arm/Group Description	All participants in the study, on both glucagon and placebo days
Measure Participants	22
Mean (Standard Deviation) [percent difference]	15.20 (14.56)

11. Secondary Outcome

Title	Number of Hypoglycemic Events (< 60 mg/dl) as Determined From BG Measurements
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of events]	0.73 (0.98)	2.59 (2.59)

12. Secondary Outcome

Title	Average BG as Determined From the Measurements Taken Before Meals and Before Bedtime
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

13. Secondary Outcome

Title	Percentage of the BG Values Taken Before Meals and Before Bedimte Less Than 70 mg/dl
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

14. Secondary Outcome

Title	Number of All BG Values Less Than 70 mg/dl
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of values]	1.45 (1.99)	4.23 (3.90)

15. Secondary Outcome

Title	Number of Study Days With Mean BG < 154 mg/dl
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of days]	4.4 (2.2)	4.2 (2.2)

16. Secondary Outcome

Title	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
Description	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.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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.

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

17. Secondary Outcome

Title	Mean BG During Exercise
Description	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

18. Secondary Outcome

Title	• Fraction of BG Values < 70 During Exercise Fraction of BG Values < 70 During Exercise
Description	Times of exercise were not collected during the study, and therefore this outcome cannot be calculated.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

19. Secondary Outcome

Title	Number of Carbohydrate Interventions for Hypoglycemia
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [number of interventions per day]	1.25 (0.48)	1.89 (0.83)

20. Secondary Outcome

Title	Total Number of Grams of Carbohydrate Taken for Hypoglycemia
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [grams per day]	23.90 (9.52)	36.29 (22.95)

21. Secondary Outcome

Title	Insulin Total Daily Dose
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [units per day]	38.7 (12.6)	37.0 (12.0)

22. Secondary Outcome

Title	• Number of Carbohydrate Interventions for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)
Description	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

23. Secondary Outcome

Title	Total Number of Grams of Carbohydrate Taken for Hypoglycemia During the Daytime (7:00 AM - 11:00 PM)
Description	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

24. Secondary Outcome

Title	Number of Carbohydrate Interventions for Hypoglycemia Overnight (11:00 PM - 7:00 AM)
Description	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

25. Secondary Outcome

Title	Total Number of Grams of Carbohydrate Taken for Hypoglycemia Overnight (11:00 PM - 7:00 AM)
Description	Timing of carbohydrate consumption for treatment of hypoglycemia was not collected during the study, so this outcome cannot be calculated
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
Measure Participants	0

26. Secondary Outcome

Title	Total Glucagon Dosing (mcg/kg/24 Hours)
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [mcg/kg/day]	6.84 (2.90)	9.8 (3.6)

27. Secondary Outcome

Title	Episodes of Nausea Per Day on Glucagon vs Placebo
Time Frame	from t=0 to study stop after 2 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Glucagon-only Bionic Pancreas	Placebo
Arm/Group Description	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.	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.
Measure Participants	22	22
Mean (Standard Deviation) [episodes of nausea per day]	1.1 (1.6)	0.4 (.07)

Adverse Events

Arm/Group Title	Glucagon-only Bionic Pancreas
Arm/Group Description	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.
All Cause Mortality
	Glucagon-only Bionic Pancreas
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Glucagon-only Bionic Pancreas
	Affected / at Risk (%)	# Events
Total	0/22 (0%)
Other (Not Including Serious) Adverse Events
	Glucagon-only Bionic Pancreas
	Affected / at Risk (%)	# Events
Total	0/22 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.