Treatment of Low Blood Sugar With Glucagon Among Patients With Type 1 Diabetes

Study Overview
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Brief Summary
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Background: Patients with type 1 diabetes (T1D) need a lifelong supply of external insulin and are advised to aim for near-normalization of blood glucose levels through intensive insulin therapy. We propose a new approach for achieving treatment goals in T1D: the combined use of insulin and glucagon, i.e. dual-hormone treatment.Only recently the prospect of treating patients with soluble glucagon has arisen and thus studies of low dose glucagon treatment of mild hypoglycemia are needed to determine whether there is clinical rationale for dual-hormone treatment of T1D. Aim: The purpose of this clinical study is to investigate the glycemic response to subcutaneous glucagon administration during mild hypoglycemia in T1D patients treated with insulin pump. Different glucagon doses are applied to determine the most appropriate dose for future dual-hormone treatment of T1D. Methods: A clinical, randomized, single blinded, crossover study will be conducted. Eight T1D patients treated with insulin pump are studied on four days. All patients are in good metabolic control (HbA1c < 7.5%), C-peptide negative and with hypoglycemia awareness. On each study day, hypoglycemia is induced with subcutaneously insulin and afterward treated with a single subcutaneous dose of glucagon. The study procedures are identical on all days except from the administered dose of glucagon (day 1: placebo, day 2: 100 ug, day 3: 200 ug, day 4: 300 ug). All patients are blinded for the glucagon dose and carry out the four days in random order. Endpoints: The present study focuses primarily on the dose related plasma glucose response of glucagon; secondary on the duration of the hyperglycemic effect of glucagon and tertiary the glucagon effect on catecholamine, cortisol, growth hormone, free fatty acids and triglycerides. The study will be conducted from august 2014.

Official Title
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Treatment of Hypoglycemia With Glucagon Among Patients With Type 1 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 1

Intervention / Treatment
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* Drug: Glucagon
* Other: Isotonic saline solution


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females aged 18-65 years Diagnosed with type 1 diabetes > 3 years HbA1c < 58 mmol/mol No appearance of autonome neuropathy Body mass index (BMI) between 20-25 kg/m2 Remained hypoglycemic awareness Insulin pump treatment > 1 year Exclusion Criteria: Allergic to glucagon or lactose Pregnancy, breast-feeding, intention of becoming pregnant, or not using adequate contraception Any disease or condition which would interfere with the subject's safety Use of a medication that significantly impacts glucose metabolism

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Isotonic Saline | Other: Isotonic saline solution<br>* Placebo<br>* Other names: 2100 København Ø;|
| Experimental: Glucagon 0.1 mg<br>GlucaGen(r) 0.1 mg administration | Drug: Glucagon<br>* Glucagon is given in three different doses according to three research days.<br>* Other names: 2880 Bagsværd;|
| Experimental: Glucagon 0.2 mg<br>GlucaGen(r) 0.2 mg administration | Drug: Glucagon<br>* Glucagon is given in three different doses according to three research days.<br>* Other names: 2880 Bagsværd;|
| Experimental: Glucagon 0.3 mg<br>GlucaGen(r) 0.3 mg administration | Drug: Glucagon<br>* Glucagon is given in three different doses according to three research days.<br>* Other names: 2880 Bagsværd;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma glucose response |  | Plasma glucose measured every five minutes after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of hyperglycemic effect of glucagon |  | Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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glucagon, insulin pump, artificial pancreas, closed-loop