Efficacy of Small Subcutaneous Glucagon Dose to Treat Hypoglycemia in Adults With Type 1 Diabetes

Phase 2

Withdrawn

Interventions: Procedure: Hypoglycaemic hyperinsulinemic clamp
Drug: Glucagon

Brief Summary: In the unfortunate case of severe hypoglycaemia, glucagon is the first-line treatment because of its potent and rapid action starting as fast as 5 minutes after subcutaneous or intramuscular injection. Large dose of glucagon such as 1 mg subcutaneous is usually associated with undesirable side-effects such as nausea, vomiting, bloating and headache.

The overall objective of this research proposal is to assess the efficacy of lower subcutaneous doses of glucagon (0.1 mg or 0.2 mg) to correct hypoglycaemia compared to the standard dose (1.0 mg) in adults with type 1 diabetes mellitus (T1D).

It is postulated that much lower dosages of glucagon (0.1 or 0.2 mg) injected subcutaneously will be just as effective as the current recommended dose of 1.0 mg to correct hypoglycaemia without the undesirable gastro-intestinal side effects.

Detailed Description: In the unfortunate case of severe hypoglycaemia, glucagon is the first-line treatment because of its potent and rapid action starting as fast as 5 minutes after subcutaneous or intramuscular injection. Current instructions for the treatment of severe hypoglycaemia call for the immediate injection of 1 mg of glucagon subcutaneously or intramuscularly. Large dose of glucagon such as 1 mg subcutaneous is usually associated with undesirable side-effects such as nausea, vomiting, bloating and headache. Moreover, glucagon emergency kits are relatively expensive (around $100 per kit), thus increasing the financial burden of diabetes on patients and the health care system.

The primary objective of this research project is to the study the pharmacological effects of different doses of glucagon injected subcutaneously to correct hypoglycaemia during controlled conditions mimicking a hypoglycaemic event in adults with type 1 diabetes. More specifically, we will be looking at the effects of subcutaneous glucagon injected at 0.1 or 0.2 mg and 1.0 mg to normalized plasma glucose during a hypoglycaemic hyperinsulinemic clamp in subjects with type 1 diabetes.

Recruitment & Eligibility

Inclusion Criteria

Exclusion Criteria

Clinically significant nephropathy (MDRD < 60 mL/min/1.73 m2).
Pregnancy
Severe hypoglycemic episode within two weeks of screening
Current use of glucocorticoid medication (except low stable dose)
Pheochromocytoma or primary adrenal insufficiency (e.g. Addison's disease)
Medical condition likely to interfere with study participation or with the ability to complete the trial by the judgment of the investigator.

Arm && Interventions

Group	Intervention	Description
Hyperinsulinemic hypoglycaemic clamp 1mg glucagon	Hypoglycaemic hyperinsulinemic clamp	A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp
Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon	Hypoglycaemic hyperinsulinemic clamp	A dose of 0.1mg or 0.2mg will be given during the hyperinsulinemic hypoglycaemic clamp.
Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon	Glucagon	A dose of 0.1mg or 0.2mg will be given during the hyperinsulinemic hypoglycaemic clamp.
Hyperinsulinemic hypoglycaemic clamp 1mg glucagon	Glucagon	A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp

Primary Outcome Measures

Name	Time	Method
Incremental area under the curve of plasma glucose concentrations	30 minutes	30-min incremental area under the curve of plasma glucose concentrations starting at the time glucagon is injected subcutaneously

Secondary Outcome Measures

Name	Time	Method
Time to reach glucose levels ≥ 4 mmol/L	Up to 2.5 hours
Time to reach glucose levels ≥ 5 mmol/L	Up to 2.5 hours
Time for 25% of glucagon appearance	Up to 2.5 hours	Time for 25% of glucagon appearance after glucagon injection
Time-to-peak plasma glucagon concentration	Up to 2.5 hours	Time-to-peak plasma glucagon concentration after glucagon injection
Time for 50% of glucagon appearance	Up to 2.5 hours	Time for 50% of glucagon appearance after glucagon injection
Time for 75% of glucagon appearance	Up to 2.5 hours	Time for 75% of glucagon appearance after glucagon injection

Locations (1): Institut de recherches cliniques de Montréal
🇨🇦
Montreal, Quebec, Canada