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

Condition(s) targeted: Type 1 Diabetes

Intervention: Hypoglycaemic hyperinsulinemic clamp (Procedure); Glucagon (Drug)

Phase: Phase 2

Status: Withdrawn

Sponsored by: Institut de Recherches Cliniques de Montreal

Official(s) and/or principal investigator(s):
Rémi Rabasa-Lhoret, Principal Investigator, Affiliation: Institut de recherches cliniques de Montréal

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.

Official title: A Double-blinded, Randomized, Two-way, Cross-over Study to Assess the Efficacy of Small Subcutaneous Glucagon Dose Against the Conventional 1 mg Dose to Treat Hypoglycemia in Adults With Type 1 Diabetes

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Primary outcome: Incremental area under the curve of plasma glucose concentrations

Secondary outcome:

Time to reach glucose levels ≥ 4 mmol/L

Time to reach glucose levels ≥ 5 mmol/L

Time-to-peak plasma glucagon concentration

Time for 25% of glucagon appearance

Time for 50% of glucagon appearance

Time for 75% of glucagon appearance

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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Males and females ≥ 18 years of old

- Clinical diagnosis of type 1 diabetes for at least two years.

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.

Institut de recherches cliniques de Montréal, Montreal, Quebec H2W 1R7, Canada

Starting date: April 2013
Last updated: December 3, 2013