Clinical trial NCT01828125: Efficacy of Small Subcutaneous Glucagon Dose to Treat Hypoglycemia in Adults With Type 1 Diabetes
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 type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Type 1 Diabetes
Keywords: Type 1 diabetes
Hypoglycemia
Glucagon
Hypoglycaemic hyperinsulinemic clamp
Lead sponsor: Institut de Recherches Cliniques de Montreal
Sponsor class: OTHER
Collaborators: name: Centre de Recherche du Centre Hospitalier de l'Université de Montréal
First posted: 2013-04-10
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Incremental area under the curve of plasma glucose concentrations
timeFrame: 30 minutes
Secondary outcomes:
measure: Time to reach glucose levels ≥ 4 mmol/L
timeFrame: Up to 2.5 hours
measure: Time to reach glucose levels ≥ 5 mmol/L
timeFrame: Up to 2.5 hours
measure: Time-to-peak plasma glucagon concentration
timeFrame: Up to 2.5 hours
measure: Time for 25% of glucagon appearance
timeFrame: Up to 2.5 hours
measure: Time for 50% of glucagon appearance
timeFrame: Up to 2.5 hours
measure: Time for 75% of glucagon appearance
timeFrame: Up to 2.5 hours
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: Institut de recherches cliniques de Montréal
state: Quebec
Study officials:
affiliation: Institut de recherches cliniques de Montréal
name: Rémi Rabasa-Lhoret
role: PRINCIPAL_INVESTIGATOR
References: