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

Study Overview
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Brief Summary
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This project focuses on development of new strategy for the prevention of exercise-associated hypoglycemia using mini-dose glucagon.

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: G-Pen Mini™ (glucagon injection)
* Other: Glucose Tabs
* Other: Basal Insulin Reduction


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 64 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control<br>No basal insulin adjustment, no carbohydrate intake (until glucose drops <70 mg/dL). | |
| Active Comparator: Basal insulin reduction<br>Basal insulin reduction to 50% five minutes before the start of exercise. | Other: Basal Insulin Reduction<br>* Basal insulin reduction to 50% 5 minutes before the start of exercise.<br>|
| Active Comparator: Glucose Tabs<br>Dextrose tabs orally (20 grams) five minutes before the start of exercise and at 30 minutes of exercise (total 40 grams). | Other: Glucose Tabs<br>* Dextrose tabs orally (20 grams) 5 minutes before the start of exercise and at 30 minutes of exercise (total 40 grams).<br>* Other names: over-the-counter oral glucose tablets;|
| Experimental: G-Pen Mini™ (glucagon injection)<br>Glucagon (150 µg) five minutes before the start of exercise (SQ-abdomen). | Drug: G-Pen Mini™ (glucagon injection)<br>* Glucagon (150 µg) 5 minutes before the start of exercise (SQ-abdomen).<br>* Other names: mini-dose glucagon;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 0 to 75 minutes following exercise initiation | 
| 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. | 0 to 75 minutes following exercise initiation | 
| Continuous Glucose Monitor (CGM) Metrics During Late Recovery - Nadir Glucose | Comparison of nadir glucose from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Peak Glucose | Comparison of peak glucose from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Mean Glucose | Comparison of mean glucose from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Coefficient of Variation | Comparison of the coefficient of variation from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Time < 54 mg/dL | Comparison of percentage of time < 54 mg/dL from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Time < 70 mg/dL | Comparison of percentage of time < 70 mg/dL from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| 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. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Time > 180 mg/dL | Comparison of percentage of time > 180 mg/dL from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 
| CGM Metrics During Late Recovery - Time > 250 mg/dL | Comparison of percentage of time > 250 mg/dL from CGM between the exercise strategies. | 90 min after the standard meal until 1200 noon the day after each exercise session | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T1D, Type 1 Diabetes, Mini-dose Glucagon, Adults, Exercise, Hypoglycemia