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

NCT01828125 | Withdrawn Phase 2

• 1 other identifier: Mini-doses glucagon
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 1 Diabetes

Keywords

Type 1 diabetes; Hypoglycemia; Glucagon; Hypoglycaemic hyperinsulinemic clamp

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (6)

• 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-to-peak plasma glucagon concentration

  Up to 2.5 hours

• Time for 25% of glucagon appearance

  Up to 2.5 hours

• Time for 50% of glucagon appearance

  Up to 2.5 hours

Study Arms (2)

Hyperinsulinemic hypoglycaemic clamp 1mg glucagon

ACTIVE COMPARATOR

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

Procedure: Hypoglycaemic hyperinsulinemic clamp; Drug: Glucagon

Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon

ACTIVE COMPARATOR

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

Procedure: Hypoglycaemic hyperinsulinemic clamp; Drug: Glucagon

Interventions

Hypoglycaemic hyperinsulinemic clamp 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.

Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon; Hyperinsulinemic hypoglycaemic clamp 1mg glucagon

Glucagon DRUG

Hyperinsulinemic hypoglycaemic clamp 0.1 or 0.2mg glucagon; Hyperinsulinemic hypoglycaemic clamp 1mg glucagon

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Males and females ≥ 18 years of old
• Clinical diagnosis of type 1 diabetes for at least two years.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherches Cliniques de Montreal: lead
• Centre de Recherche du Centre Hospitalier de l'Université de Montréal: collaborator

Study Sites (1)

Institut de recherches cliniques de Montréal

Montreal, Quebec, H2W 1R7, Canada

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Hypoglycemia

Interventions

Glucagon

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Proglucagon; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Rémi Rabasa-Lhoret

  Institut de recherches cliniques de Montréal

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate professor of Medicine

Study Record Dates

• First Submitted: April 2, 2013
• First Posted: April 10, 2013
• Study Start: April 1, 2013
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: December 4, 2013

Record last verified: 2013-12

Locations

CA (1)