Back to resultsThe Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
G-Pen Mini™ (glucagon injection)
Glucose Tabs
Basal Insulin Reduction
Sponsored by
About this trial
This is an interventional prevention trial for Diabetes Mellitus, Type 1 focused on measuring T1D, Type 1 Diabetes, Mini-dose Glucagon, Adults, Exercise, Hypoglycemia
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin
- Age 18-<65 years
- Duration of T1D ≥ 2 years
- Random C-peptide < 0.6 ng/ml
- Using continuous subcutaneous insulin infusion (CSII; insulin pump) for at least 6 months, with no plans to discontinue pump use during the study
- Exercises regularly, i.e. ≥30 minutes moderate or more vigorous aerobic activity X ≥3 times/week
- Body mass index (BMI) <30 kg/m2
Females must meet one of the following criteria:
- Of childbearing potential and not currently pregnant or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study; or
- Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
- In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
- Willing to adhere to the protocol requirements for the duration of the study
- Must be enrolled in the T1D Exchange clinic registry or willing to join the registry
Exclusion Criteria:
- One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment)
- Active diabetic retinopathy (proliferative diabetic retinopathy or vitreous hemorrhage in past 6 months) that could potentially be worsened by exercise protocol
- Peripheral neuropathy with insensate feet
- Cardiovascular autonomic neuropathy with inappropriate heart rate response to exercise
- Use of non-insulin anti-diabetic medications
- Use of beta-blockers
- Use of agents that affect hepatic glucose production such as beta adrenergic agonists, xanthine derivatives
- Use of Pramlintide
- Currently following a very low calorie or other weight-loss diet
- Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study
Sites / Locations
- Joslin Diabetes Center
- University of Pennsylvania
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
No Intervention
Active Comparator
Active Comparator
Experimental
Arm Label
Control
Basal insulin reduction
Glucose Tabs
G-Pen Mini™ (glucagon injection)
Arm 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).
Outcomes
Primary Outcome Measures
Glycemic Response During Exercise and Early Recovery
Comparison of glycemic response (from blood glucose) during exercise and early recovery between each exercise strategy.
Secondary Outcome Measures
Number of Participants With Hypoglycemia (<70 mg/dL) During Exercise and Early Recovery
Comparison of occurrence of hypoglycemia (<70 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
Number of Participants With Hyperglycemia (≥250 mg/dL) During Exercise and Early Recovery
Comparison of occurrence of hyperglycemia (≥250 mg/dL from blood glucose) during exercise and early recovery between each exercise strategy.
Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose
Comparison of nadir glucose from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Peak Glucose
Comparison of peak glucose from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Mean Glucose
Comparison of mean glucose from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Coefficient of Variation
Comparison of the coefficient of variation from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Time < 54 mg/dL
Comparison of percentage of time < 54 mg/dL from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Time < 70 mg/dL
Comparison of percentage of time < 70 mg/dL from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Time in Range (70-180 mg/dL)
Comparison of percentage of time in range (70-180 mg/dL) from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Time > 180 mg/dL
Comparison of percentage of time > 180 mg/dL from CGM between the exercise strategies.
CGM Metrics During Late Recovery - Time > 250 mg/dL
Comparison of percentage of time > 250 mg/dL from CGM between the exercise strategies.
Full Information
NCT ID
NCT02660242
First Posted
January 6, 2016
Last Updated
February 28, 2020
Sponsor
Jaeb Center for Health Research
Collaborators
Xeris Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT02660242
Brief Title
The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Official Title
The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
February 2020
Overall Recruitment Status
Completed
Study Start Date
January 2016 (undefined)
Primary Completion Date
February 15, 2017 (Actual)
Study Completion Date
February 15, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Jaeb Center for Health Research
Collaborators
Xeris Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
This project focuses on development of new strategy for the prevention of exercise-associated hypoglycemia using mini-dose glucagon.
Detailed Description
The primary objective of the protocol is to determine if the administration of mini-dose glucagon administered subcutaneously just before exercise produces better glucose stability than no adjustments for moderate intensity exercise in patients with Type 1 Diabetes (T1D). It will also be assessed whether mini-dose glucagon before exercise produces better glucose stability than basal insulin reductions or extra carbohydrate consumption.
This is a randomized, 4-way crossover trial. The trial will include 16 participants who complete the study.
Each participant will undergo four aerobic exercise sessions (in random order), with different strategies for glucose regulation:
Control Trial: Fasted exercise, no basal insulin reduction
Strategy 1: Fasted exercise, basal insulin reduction only (50% reduction in basal rate at 60 minutes before exercise, for the duration of the exercise)
Strategy 2: Fasted exercise, no basal adjustment + pre-exercise glucose tabs (buccal route-40 grams in total )
Strategy 3: Fasted exercise, no basal adjustment + pre-exercise mini-dose glucagon (sc)
In all 4 sessions, aerobic exercise will be performed in the fasted state (before a standardized meal) for 45 minuets at ~50-55% of the participant's per-determined aerobic capacity. The participant's pump will be blinded during the control trial, strategy 1, and strategy 3 and an injection of saline will be given during the control trial and strategy 1 so that participant is blinded to strategy.
The primary outcome for this study will be the glycemic response during exercise and early recovery.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
T1D, Type 1 Diabetes, Mini-dose Glucagon, Adults, Exercise, Hypoglycemia
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Participant
Allocation
Randomized
Enrollment
16 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Control
Arm Type
No Intervention
Arm Description
No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL).
Arm Title
Basal insulin reduction
Arm Type
Active Comparator
Arm Description
Basal insulin reduction to 50% five minutes before the start of exercise.
Arm Title
Glucose Tabs
Arm Type
Active Comparator
Arm Description
Dextrose tabs orally (20 grams) five minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).
Arm Title
G-Pen Mini™ (glucagon injection)
Arm Type
Experimental
Arm Description
Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen).
Intervention Type
Drug
Intervention Name(s)
G-Pen Mini™ (glucagon injection)
Other Intervention Name(s)
mini-dose glucagon
Intervention Description
Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).
Intervention Type
Other
Intervention Name(s)
Glucose Tabs
Other Intervention Name(s)
over-the-counter oral glucose tablets
Intervention Description
Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).
Intervention Type
Other
Intervention Name(s)
Basal Insulin Reduction
Intervention Description
Basal insulin reduction to 50% 5 minutes before the start of exercise.
Primary Outcome Measure Information:
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)
Secondary Outcome Measure Information:
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
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
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
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
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
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
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
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
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
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
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of presumed autoimmune type 1 diabetes, receiving daily insulin
Age 18-<65 years
Duration of T1D ≥ 2 years
Random C-peptide < 0.6 ng/ml
Using continuous subcutaneous insulin infusion (CSII; insulin pump) for at least 6 months, with no plans to discontinue pump use during the study
Exercises regularly, i.e. ≥30 minutes moderate or more vigorous aerobic activity X ≥3 times/week
Body mass index (BMI) <30 kg/m2
Females must meet one of the following criteria:
Of childbearing potential and not currently pregnant or lactating, and agrees to use an accepted contraceptive regimen as described in the study procedure manual throughout the entire duration of the study; or
Of non-childbearing potential, defined as a female who has had a hysterectomy or tubal ligation, is clinically considered infertile or is in a menopausal state (at least 1 year without menses)
In good general health with no conditions that could influence the outcome of the trial, and in the judgment of the investigator is a good candidate for the study based on review of available medical history, physical examination and clinical laboratory evaluations
Willing to adhere to the protocol requirements for the duration of the study
Must be enrolled in the T1D Exchange clinic registry or willing to join the registry
Exclusion Criteria:
One or more severe hypoglycemic episodes in the past 12 months (as defined by an episode that required third party assistance for treatment)
Active diabetic retinopathy (proliferative diabetic retinopathy or vitreous hemorrhage in past 6 months) that could potentially be worsened by exercise protocol
Peripheral neuropathy with insensate feet
Cardiovascular autonomic neuropathy with inappropriate heart rate response to exercise
Use of non-insulin anti-diabetic medications
Use of beta-blockers
Use of agents that affect hepatic glucose production such as beta adrenergic agonists, xanthine derivatives
Use of Pramlintide
Currently following a very low calorie or other weight-loss diet
Participation in other studies involving administration of an investigational drug or device within 30 days or 5 half-lives, whichever is longer, before screening for the current study or planning to participate in another such study during participation in the current study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michael Riddell, PhD
Organizational Affiliation
York University
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Michael Rickels, M.D., M.S.
Organizational Affiliation
University of Pennsylvania
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Howard Wolpert, M.D.
Organizational Affiliation
Joslin Diabetes Center
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Stephanie DuBose, M.P.H
Organizational Affiliation
Jaeb Center for Health Research
Official's Role
Principal Investigator
Facility Information:
Facility Name
Joslin Diabetes Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
12. IPD Sharing Statement
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21673486
Citation
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The Use of Mini-dose Glucagon to Prevent Exercise-induced Hypoglycemia in Type 1 Diabetes
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