Low-dose Glucagon for Prevention of Exercise-Induced Hypoglycemia in People With Type 1 Diabetes

Study Overview
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Brief Summary
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The primary aim of the study is to compare the efficacy of single-administration low-dose glucagon and split-administration low-dose glucagon to placebo for prevention of exercise-induced hypoglycemia in people with type 1 diabetes using insulin pumps and multiple daily injections (MDI). The secondary aim is to compare the accuracy of three continuous glucose monitors (CGM) during and after exercise in inpatient and outpatient settings.

Detailed Description
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A randomized, single-blinded, placebo-controlled three-arm cross-over study will be conducted to assess the study objectives. 22 participants with type 1 diabetes will complete three study visits in random order. At every visit the participants will exercise for 60 min receiving different low doses of glucagon before or before and after exercise compared with placebo. During the visits and in an outpatient period the participants will have 3 different CGM devices installed and the values will be compared with self-monitored blood glucose values.

Official Title
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Low-dose Glucagon for Prevention of Exercise-Induced Hypoglycemia in People With Type 1 Diabetes

Conditions
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Type 1 Diabetes, Hypoglycemia

Intervention / Treatment
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* Drug: GlucaGen
* Drug: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 T1D ≥ 2 years Use of insulin pump or MDI therapy for ≥ 6 months Current use of insulin aspart HbA1c ≤ 70mmol/mol (8.5%) Body mass index (BMI) ≤ 30 kg/m2 Performs exercise ≥1 time per week Exclusion Criteria: Use of anti-diabetic medicine (other than insulin), corticosteroids or other drugs affecting glucose metabolism during the study period and within 30 days prior to study start Professional athletes or highly active individuals ( ≥ 5 hours of exercise per week) Known or suspected allergies to glucagon or related products History of hypersensitivity or allergic reaction to glucagon or lactose Allergy to the patch of the CGM devices Patients with pheochromocytoma, insulinoma or gastroparesis Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant or are not using adequate contraceptive methods (methods are considered adequate for study enrollment for females: an intrauterine device, hormonal contraception (birth control pills, implant, patch, vaginal ring or injection), a single partner who is sterile or infertile, or sexual abstinence. Contraception is required throughout the study duration. Sterilized or postmenopausal women (>12 months since last period) are not required to use contraception) Inability to understand the individual information and to give informed consent Current participation in another clinical trial that, in the judgment of the investigator, will compromise the results of the study or the safety of the subject Concomitant medical or psychological conditions identified through review of medical history, physical examination and clinical laboratory analysis that, according to the investigator's assessment, makes the individual unsuitable for study participation

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: A randomized, single-blinded, placebo-controlled three-arm cross-over study
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 150 ug glucagon before exercise<br>150 ug glucagon will be administered subcutaneously just before exercise and placebo will be administered after exercise. | Drug: GlucaGen<br>* 150 ug or 75*2 ug glucagon will be administered subcutaneously to the participants before and after exercise.<br>* Other names: Glucagon, GlucaGen®, Novo Nordisk, ATC code H04AA01;|
| Experimental: 2*75 ug glucagon before exercise and after exercise<br>75 ug glucagon will be administered subcutaneously just before exercise and another 75 ug of glucagon will be administered immediately after exercise. | Drug: GlucaGen<br>* 150 ug or 75*2 ug glucagon will be administered subcutaneously to the participants before and after exercise.<br>* Other names: Glucagon, GlucaGen®, Novo Nordisk, ATC code H04AA01;|
| Active Comparator: Saline as placebo<br>Saline as placebo will be administered in the same amount as glucagon before and after exercise. | Drug: Saline<br>* Saline will be used as placebo before and after exercise.<br>* Other names: ATC-code: Natriumklorid isotonisk BAUER B05BB01, V07AB;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence rate of hypoglycemia (PG < 3.9 mmol/l) |  | From 0-180 minutes post-intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of time below range (PG < 3.9) |  | From 0-180 minutes post-intervention | 
| Percentage of time in range (PG ≥ 3.9 mmol/l and ≤ 10.0 mmol/l) |  | From 0-180 minutes post-intervention | 
| Time (min) to hypoglycemia (PG < 3.9 mmol/l) |  | From 0-180 minutes post-intervention | 
| Change in plasma glucose levels |  | From 0-180 minutes post-intervention | 
| Incidence rate of hyperglycemia (PG > 10 mmol/l) |  | From 0-180 minutes post-intervention | 
| Nadir plasma glucose concentration |  | From 0-180 minutes post-intervention | 
| Peak plasma glucose concentration |  | From 0-180 minutes post-intervention | 
| Incremental peak in plasma glucose concentration |  | From 0-180 minutes post-intervention | 
| Mean plasma glucose concentration |  | From 0-180 minutes post-intervention | 
| Plasma glucose Area Under the Curve (AUC) |  | From 0 to 180 min post-intervention | 
| Percentage of time in hyperglycemia (PG > 10 mmol/l) |  | From 0-180 minutes post-intervention | 
| Change in visual analogue scale (VAS) for nausea, headache, stomachache, injection site pain and palpitations from intervention (tintervention = 0) to 180 min post-intervention |  | From 0-180 minutes post-intervention | 
| Mean absolute relative difference (MARD) during the 60-minutes exercise session (using SMBG as the reference value) |  | During exercise | 
| MARD during the three-day outpatient period (using the 5 daily SMBG as the reference value) |  | During the three-day outpatient period | 
| MARD during the three-hour inpatient study visit (using YSI as reference value) |  | During exercise | 
| Rate-of change (ROC) accuracy (using SMBG and YSI as the reference value) |  | During exercise and during the three-day outpatient period | 
| Point accuracy with the Clarke Error Grid Analysis (CEGA) (using SMBG and YSI as the reference value) |  | During exercise and during the three-day outpatient period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 1 Diabetes, Exercise, Hypoglycemia, Glucagon, Continuous Glucose Monitoring