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

Type 1 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01828125
• Other study ID #: Mini-doses glucagon
• Status: Withdrawn
• Phase: Phase 2
• First received: April 2, 2013
• Last updated: December 3, 2013
• Start date: April 2013
• Est. completion date: December 2013

Study information

• Verified date: December 2013
• Source: Institut de Recherches Cliniques de Montreal
• Contact: n/a
• Is FDA regulated: No
• Health authority: Canada: Ethics Review Committee
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

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

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1
• Hypoglycemia
• Type 1 Diabetes

Intervention

Procedure:
• Hypoglycaemic hyperinsulinemic clamp
A first catheter will be inserted for infusion of D-[6,6-2H2] glucose and insulin. A second catheter will be inserted for infusion of dextrose. Dextrose infusion will be enriched with D-[6,6-2H2] glucose. A third catheter will be inserted for sampling. D-[6,6-2H2] glucose will be administered as a priming dose followed by a constant infusion throughout the experiment. Insulin will be administered as a primed continuous infusion. The first two hours will serve as an equilibration period for the tracer while glucose infusion will be adjusted to achieve a plasma glucose concentration of 5 mmol/L. The third hour is considered the baseline period. Following this, dextrose infusion rate will be decreased over a period of 1 hour to attain hypoglycaemia with a target blood glucose level at 2.8 mmol/L. At the end of the fourth hour, a subcutaneous glucagon dose will be given and plasma samples will be drawn for the determination of labelled and unlabelled glucose, plasma insulin and glucagon.

Drug:
• Glucagon

Locations

Country	Name	City	State
Canada	Institut de recherches cliniques de Montréal	Montreal	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Cliniques de Montreal	Centre de Recherche du Centre Hospitalier de l'Université de Montréal

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incremental area under the curve of plasma glucose concentrations	30-min incremental area under the curve of plasma glucose concentrations starting at the time glucagon is injected subcutaneously	30 minutes	No
Secondary	Time to reach glucose levels = 4 mmol/L		Up to 2.5 hours	No
Secondary	Time to reach glucose levels = 5 mmol/L		Up to 2.5 hours	No
Secondary	Time-to-peak plasma glucagon concentration	Time-to-peak plasma glucagon concentration after glucagon injection	Up to 2.5 hours	No
Secondary	Time for 25% of glucagon appearance	Time for 25% of glucagon appearance after glucagon injection	Up to 2.5 hours	No
Secondary	Time for 50% of glucagon appearance	Time for 50% of glucagon appearance after glucagon injection	Up to 2.5 hours	No
Secondary	Time for 75% of glucagon appearance	Time for 75% of glucagon appearance after glucagon injection	Up to 2.5 hours	No