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
Trial Snapshot
- Phase
- Phase 2
- Status
- Withdrawn
- Sponsor
- Locations
- 1
- Primary Endpoint
- Incremental area under the curve of plasma glucose concentrations
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Care Provider)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Hyperinsulinemic hypoglycaemic clamp 1mg glucagon
A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp
Intervention: Hypoglycaemic hyperinsulinemic clamp (Procedure)
Hyperinsulinemic hypoglycaemic clamp 1mg glucagon
A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp
Intervention: Glucagon (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.
Intervention: Hypoglycaemic hyperinsulinemic clamp (Procedure)
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.
Intervention: Glucagon (Drug)
Outcomes
Primary Outcomes
Incremental area under the curve of plasma glucose concentrations
Time Frame: 30 minutes
30-min incremental area under the curve of plasma glucose concentrations starting at the time glucagon is injected subcutaneously
Secondary Outcomes
- 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 for 25% of glucagon appearance(Up to 2.5 hours)
- Time-to-peak plasma glucagon concentration(Up to 2.5 hours)
- Time for 50% of glucagon appearance(Up to 2.5 hours)
- Time for 75% of glucagon appearance(Up to 2.5 hours)
Investigators
Rémi Rabasa-Lhoret
Associate professor of Medicine
Institut de Recherches Cliniques de Montreal