The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes

• ClinicalTrials.gov Identifier: NCT02660242
• Recruitment Status: Completed
• First Posted: January 21, 2016
• Results First Posted: August 7, 2018
• Last Update Posted: March 3, 2020
• Sponsor: Jaeb Center for Health Research
• Collaborator: Xeris Pharmaceuticals
• Information provided by (Responsible Party): Jaeb Center for Health Research

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Single (Participant); Primary Purpose: Prevention
• Condition: Diabetes Mellitus, Type 1
• Interventions: Drug: G-Pen Mini™ (glucagon injection); Other: Glucose Tabs; Other: Basal Insulin Reduction
• Enrollment: 16

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	MIni-dose Glucagon Crossover Trial
Arm/Group Description	Each participant will undergo four aerobic exercise sessions (in random order) of a) a Control Trial: Fasted exercise, no basal insulin reduction; b) Strategy 1: Fasted exercise, basal insulin reduction only (50% reduction in basal rate five minutes before exercise, for the duration of the exercise); c) Strategy 2: Fasted exercise, no basal adjustment + pre-exercise and mid-exercise glucose tabs (buccal route-40 grams in total); d) Strategy 3: Fasted exercise, no basal adjustment + pre-exercise mini-dose glucagon (sc). Each period includes 0-165 minutes in the lab and the participant continues to wear a continuous glucose monitor during the afternoon, overnight, and through noon the following day.
Period Title: Control
Started	16
Completed	16
Not Completed	0
Period Title: Basal Insulin Reduction
Started	16
Completed	16
Not Completed	0
Period Title: Glucose Tabs
Started	16 [1]
Completed	15
Not Completed	1
Reason Not Completed
Lost to Follow-up	1
[1] 16 participants were randomized but only 15 completed all 4 periods.
Period Title: Glucagon Injection
Started	16 [1]
Completed	15
Not Completed	1
Reason Not Completed
Lost to Follow-up	1
[1] 16 participants were randomized but only 15 completed all 4 periods.

Baseline Characteristics

Arm/Group Title		Entire Study Population
Arm/Group Description		Includes all patients who completed the crossover trial.
Overall Number of Baseline Participants		15
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	15 participants
		30; (25 to 43)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	Female	6 40.0%
	Male	9 60.0%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	Hispanic or Latino	2 13.3%
	Not Hispanic or Latino	12 80.0%
	Unknown or Not Reported	1 6.7%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants
	American Indian or Alaska Native	0 0.0%
	Asian	1 6.7%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	0 0.0%
	White	14 93.3%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Type 1 Diabetes Duration, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	15 participants
		22; (14 to 31)
HbA1c; Median (Inter-Quartile Range); Unit of measure: %
	Number Analyzed	15 participants
		6.8; (6.5 to 7.6)
Body Mass Index (BMI); Median (Inter-Quartile Range); Unit of measure: Kg/m^2
	Number Analyzed	15 participants
		24; (23 to 27)
VO2Max; Median (Inter-Quartile Range); Unit of measure: mL/kg/min
	Number Analyzed	15 participants
		42; (35 to 51)

Outcome Measures

1. Primary Outcome

Title	Glycemic Response During Exercise and Early Recovery
Description	Comparison of glycemic response (from blood glucose) during exercise and early recovery between each exercise strategy.
Time Frame	0 to 75 minutes following exercise initiation (0, 5, 10, 15, 25, 35, 45, 50, 55, 60, 75 min)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	15	15	15	15
Mean (Standard Deviation); Unit of Measure: mg/dL
Plasma Glucose Concentration (End of Exercise)	86 (30)	85 (25)	174 (59)	161 (39)
Plasma Glucose Concentration (End Early Recovery)	90 (34)	92 (34)	222 (66)	163 (49)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	The mini-dose glucagon (MDG) condition was compared with each of the conditions. In the event that exercise was terminated early due to glucose <70 mg/dL and the participant was treated for hypoglycemia (or if participant was treated for hypoglycemia during early recovery [prior to the meal]), the nadir glucose value was carried forward through the end of early recovery.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Mixed model w/ repeated measures to account for correlation from cross-over design and multiple measures, adjusting for baseline glucose and period.

2. Secondary Outcome

Title	Number of Participants With Hypoglycemia (<70 mg/dL) During Exercise and Early Recovery
Description	Comparison of occurrence of hypoglycemia (<70 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
Time Frame	0 to 75 minutes following exercise initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	15	15	15	15
Measure Type: Count of Participants; Unit of Measure: Participants
	6 40.0%	5 33.3%	0 0.0%	0 0.0%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.99
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Adjusted for subject effect, exercise session, and baseline blood glucose

3. Secondary Outcome

Title	Number of Participants With Hyperglycemia (≥250 mg/dL) During Exercise and Early Recovery
Description	Comparison of occurrence of hyperglycemia (≥250 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
Time Frame	0 to 75 minutes following exercise initiation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	15	15	15	15
Measure Type: Count of Participants; Unit of Measure: Participants
	0 0.0%	0 0.0%	5 33.3%	1 6.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.15
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Adjusted for subject effect, exercise session, and baseline blood glucose

4. Secondary Outcome

Title	Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose
Description	Comparison of nadir glucose from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data.

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% five minutes before the start of exercise.	Dextrose tabs orally (20 grams) five minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Median (Inter-Quartile Range); Unit of Measure: mg/dL
	45; (39 to 60)	44; (40 to 56)	49; (40 to 55)	51; (40 to 53)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.99
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

5. Secondary Outcome

Title	CGM Metrics During Late Recovery - Peak Glucose
Description	Comparison of peak glucose from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data.

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Median (Inter-Quartile Range); Unit of Measure: mg/dL
	241; (216 to 279)	239; (222 to 299)	267; (211 to 331)	269; (235 to 281)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.43
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

6. Secondary Outcome

Title	CGM Metrics During Late Recovery - Mean Glucose
Description	Comparison of mean glucose from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data.

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Median (Inter-Quartile Range); Unit of Measure: mg/dL
	129; (114 to 144)	139; (127 to 149)	130; (117 to 148)	147; (126 to 161)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.16
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

7. Secondary Outcome

Title	CGM Metrics During Late Recovery - Coefficient of Variation
Description	Comparison of the coefficient of variation from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Median (Inter-Quartile Range); Unit of Measure: percentage
	32; (29 to 42)	35; (33 to 40)	36; (32 to 42)	33; (31 to 35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.69
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

8. Secondary Outcome

Title	CGM Metrics During Late Recovery - Time < 54 mg/dL
Description	Comparison of percentage of time < 54 mg/dL from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Mean (Standard Deviation); Unit of Measure: percentage
	3 (3)	3 (3)	3 (1)	2 (2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.67
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

9. Secondary Outcome

Title	CGM Metrics During Late Recovery - Time < 70 mg/dL
Description	Comparison of percentage of time < 70 mg/dL from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Mean (Standard Deviation); Unit of Measure: percentage
	10 (9)	8 (6)	8 (6)	6 (4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.84
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

10. Secondary Outcome

Title	CGM Metrics During Late Recovery - Time in Range (70-180 mg/dL)
Description	Comparison of percentage of time in range (70-180 mg/dL) from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Mean (Standard Deviation); Unit of Measure: percentage
	73 (12)	71 (10)	69 (20)	67 (15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.63
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

11. Secondary Outcome

Title	CGM Metrics During Late Recovery - Time > 180 mg/dL
Description	Comparison of percentage of time > 180 mg/dL from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Mean (Standard Deviation); Unit of Measure: percentage
	16 (13)	21 (12)	23 (20)	26 (16)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.24
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

12. Secondary Outcome

Title	CGM Metrics During Late Recovery - Time > 250 mg/dL
Description	Comparison of percentage of time > 250 mg/dL from CGM between the exercise strategies.
Time Frame	90 min after the standard meal until 1200 noon the day after each exercise session

Outcome Measure Data

Analysis Population Description

Included data were limited to periods with at least 12 hours of CGM data

Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description:	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Overall Number of Participants Analyzed	14	13	13	14
Mean (Standard Deviation); Unit of Measure: percentage
	1 (2)	4 (9)	9 (17)	5 (7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Control, Basal Insulin Reduction, Glucose Tabs, G-Pen Mini™ (Glucagon Injection)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.26
	Comments	[Not Specified]
	Method	Mixed Models Analysis
	Comments	Accounted for correlation due to cross-over design and adjusted for exercise session

Adverse Events

Time Frame	Adverse Events (AE) were collected 12 hours prior to each exercise session, during each exercise session, and during the day after each exercise session.
Adverse Event Reporting Description	Hypoglycemia, hyperglycemia, injection-related, and exercise-induced events only reported as AEs when criteria below met. Hypoglycemia: event required dextrose or glucagon to treat; Hyperglycemia: evaluation or treatment obtained from a health care provider or event involved Diabetic Ketoacidosis; Injection-related events: treatment was given; Exercise-induced events: subject falls or has signs of heart attack, poor perfusion, angina, pathologic arrhythmia, or other condition not expected
Arm/Group Title	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
Arm/Group Description	No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).	Basal insulin reduction to 50% 5 minutes before the start of exercise.	Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).	Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
All-Cause Mortality
	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)
Serious Adverse Events
	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Control	Basal Insulin Reduction	Glucose Tabs	G-Pen Mini™ (Glucagon Injection)
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)	0/15 (0.00%)

Limitations and 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.

Results Point of Contact

• Name/Title: Stephanie DuBose
• Organization: Jaeb Center for Health Research
• Phone: 813.975.8690
• EMail: sdubose@jaeb.org

Publications:

Chu L, Hamilton J, Riddell MC. Clinical management of the physically active patient with type 1 diabetes. Phys Sportsmed. 2011 May;39(2):64-77. doi: 10.3810/psm.2011.05.1896.

West DJ, Morton RD, Bain SC, Stephens JW, Bracken RM. Blood glucose responses to reductions in pre-exercise rapid-acting insulin for 24 h after running in individuals with type 1 diabetes. J Sports Sci. 2010 May;28(7):781-8. doi: 10.1080/02640411003734093.

Brazeau AS, Rabasa-Lhoret R, Strychar I, Mircescu H. Barriers to physical activity among patients with type 1 diabetes. Diabetes Care. 2008 Nov;31(11):2108-9. doi: 10.2337/dc08-0720. Epub 2008 Aug 8.

Rabasa-Lhoret R, Bourque J, Ducros F, Chiasson JL. Guidelines for premeal insulin dose reduction for postprandial exercise of different intensities and durations in type 1 diabetic subjects treated intensively with a basal-bolus insulin regimen (ultralente-lispro). Diabetes Care. 2001 Apr;24(4):625-30. doi: 10.2337/diacare.24.4.625.

Campbell MD, Walker M, Trenell MI, Jakovljevic DG, Stevenson EJ, Bracken RM, Bain SC, West DJ. Large pre- and postexercise rapid-acting insulin reductions preserve glycemia and prevent early- but not late-onset hypoglycemia in patients with type 1 diabetes. Diabetes Care. 2013 Aug;36(8):2217-24. doi: 10.2337/dc12-2467. Epub 2013 Mar 20.

Stenerson M, Cameron F, Payne SR, Payne SL, Ly TT, Wilson DM, Buckingham BA. The impact of accelerometer use in exercise-associated hypoglycemia prevention in type 1 diabetes. J Diabetes Sci Technol. 2015 Jan;9(1):80-5. doi: 10.1177/1932296814551045. Epub 2014 Sep 17.

Tsalikian E, Mauras N, Beck RW, Tamborlane WV, Janz KF, Chase HP, Wysocki T, Weinzimer SA, Buckingham BA, Kollman C, Xing D, Ruedy KJ; Diabetes Research In Children Network Direcnet Study Group. Impact of exercise on overnight glycemic control in children with type 1 diabetes mellitus. J Pediatr. 2005 Oct;147(4):528-34. doi: 10.1016/j.jpeds.2005.04.065.

Tanenberg RJ, Newton CA, Drake AJ. Confirmation of hypoglycemia in the "dead-in-bed" syndrome, as captured by a retrospective continuous glucose monitoring system. Endocr Pract. 2010 Mar-Apr;16(2):244-8. doi: 10.4158/EP09260.CR.

Campbell MD, Walker M, Trenell MI, Luzio S, Dunseath G, Tuner D, Bracken RM, Bain SC, Russell M, Stevenson EJ, West DJ. Metabolic implications when employing heavy pre- and post-exercise rapid-acting insulin reductions to prevent hypoglycaemia in type 1 diabetes patients: a randomised clinical trial. PLoS One. 2014 May 23;9(5):e97143. doi: 10.1371/journal.pone.0097143. eCollection 2014.

Taplin CE, Cobry E, Messer L, McFann K, Chase HP, Fiallo-Scharer R. Preventing post-exercise nocturnal hypoglycemia in children with type 1 diabetes. J Pediatr. 2010 Nov;157(5):784-8.e1. doi: 10.1016/j.jpeds.2010.06.004. Epub 2010 Jul 21.

Riddell MC, Bar-Or O, Ayub BV, Calvert RE, Heigenhauser GJ. Glucose ingestion matched with total carbohydrate utilization attenuates hypoglycemia during exercise in adolescents with IDDM. Int J Sport Nutr. 1999 Mar;9(1):24-34. doi: 10.1123/ijsn.9.1.24.

Robertson K, Riddell MC, Guinhouya BC, Adolfsson P, Hanas R; International Society for Pediatric and Adolescent Diabetes. ISPAD Clinical Practice Consensus Guidelines 2014. Exercise in children and adolescents with diabetes. Pediatr Diabetes. 2014 Sep;15 Suppl 20:203-23. doi: 10.1111/pedi.12176. No abstract available.

Camacho RC, Galassetti P, Davis SN, Wasserman DH. Glucoregulation during and after exercise in health and insulin-dependent diabetes. Exerc Sport Sci Rev. 2005 Jan;33(1):17-23.

Oskarsson PR, Lins PE, Wallberg Henriksson H, Adamson UC. Metabolic and hormonal responses to exercise in type 1 diabetic patients during continuous subcutaneous, as compared to continuous intraperitoneal, insulin infusion. Diabetes Metab. 1999 Dec;25(6):491-7.

Haymond MW, Schreiner B. Mini-dose glucagon rescue for hypoglycemia in children with type 1 diabetes. Diabetes Care. 2001 Apr;24(4):643-5. doi: 10.2337/diacare.24.4.643.

Diabetes Research in Children Network (DirecNet) Study Group; Tsalikian E, Kollman C, Tamborlane WB, Beck RW, Fiallo-Scharer R, Fox L, Janz KF, Ruedy KJ, Wilson D, Xing D, Weinzimer SA. Prevention of hypoglycemia during exercise in children with type 1 diabetes by suspending basal insulin. Diabetes Care. 2006 Oct;29(10):2200-4. doi: 10.2337/dc06-0495.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rickels MR, DuBose SN, Toschi E, Beck RW, Verdejo AS, Wolpert H, Cummins MJ, Newswanger B, Riddell MC; T1D Exchange Mini-Dose Glucagon Exercise Study Group. Mini-Dose Glucagon as a Novel Approach to Prevent Exercise-Induced Hypoglycemia in Type 1 Diabetes. Diabetes Care. 2018 Sep;41(9):1909-1916. doi: 10.2337/dc18-0051. Epub 2018 May 18.

• Responsible Party: Jaeb Center for Health Research
• ClinicalTrials.gov Identifier: NCT02660242
• Other Study ID Numbers: T1DX Mini-dose Exercise
• First Submitted: January 6, 2016
• First Posted: January 21, 2016
• Results First Submitted: June 6, 2018
• Results First Posted: August 7, 2018
• Last Update Posted: March 3, 2020