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

NCT ID: NCT01828125

Last Updated: 2013-12-04

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2013-12-31

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Hypoglycemia; Glucagon; Hypoglycaemic hyperinsulinemic clamp

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Hyperinsulinemic hypoglycaemic clamp 1mg glucagon

A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp

Group Type: ACTIVE_COMPARATOR

Hypoglycaemic hyperinsulinemic clamp

Intervention Type: PROCEDURE

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.

Glucagon

Intervention Type: DRUG

Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon

A dose of 0.1mg or 0.2mg will be given during the hyperinsulinemic hypoglycaemic clamp.

Group Type: ACTIVE_COMPARATOR

Hypoglycaemic hyperinsulinemic clamp

Intervention Type: PROCEDURE

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.

Glucagon

Intervention Type: DRUG

Interventions

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.

Intervention Type: PROCEDURE

Glucagon

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre de Recherche du Centre Hospitalier de l'Université de Montréal

OTHER

Sponsor Role: collaborator

Institut de Recherches Cliniques de Montreal

OTHER

Sponsor Role: lead

Responsible Party

Rémi Rabasa-Lhoret

Associate professor of Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Rémi Rabasa-Lhoret

Role: PRINCIPAL_INVESTIGATOR

Institut de recherches cliniques de Montréal

Locations

Institut de recherches cliniques de Montréal

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

Mini-doses glucagon

Identifier Type: -

Identifier Source: org_study_id