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

This study has been withdrawn prior to enrollment.
Sponsor:
Collaborator:
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Information provided by (Responsible Party):
Rémi Rabasa-Lhoret, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier:
NCT01828125
First received: April 2, 2013
Last updated: December 3, 2013
Last verified: December 2013
  Purpose

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.


Condition Intervention Phase
Type 1 Diabetes
Procedure: Hypoglycaemic hyperinsulinemic clamp
Drug: Glucagon
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Institut de Recherches Cliniques de Montreal:

Primary Outcome Measures:
  • Incremental area under the curve of plasma glucose concentrations [ Time Frame: 30 minutes ] [ Designated as safety issue: No ]
    30-min incremental area under the curve of plasma glucose concentrations starting at the time glucagon is injected subcutaneously


Secondary Outcome Measures:
  • Time to reach glucose levels ≥ 4 mmol/L [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
  • Time to reach glucose levels ≥ 5 mmol/L [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
  • Time-to-peak plasma glucagon concentration [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
    Time-to-peak plasma glucagon concentration after glucagon injection

  • Time for 25% of glucagon appearance [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
    Time for 25% of glucagon appearance after glucagon injection

  • Time for 50% of glucagon appearance [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
    Time for 50% of glucagon appearance after glucagon injection

  • Time for 75% of glucagon appearance [ Time Frame: Up to 2.5 hours ] [ Designated as safety issue: No ]
    Time for 75% of glucagon appearance after glucagon injection


Enrollment: 0
Study Start Date: April 2013
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hyperinsulinemic hypoglycaemic clamp 1mg glucagon
A 1.0mg glucagon dose will be given during the hyperinsulinemic hypoglycaemic clamp
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
Active Comparator: 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.
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

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01828125

Locations
Canada, Quebec
Institut de recherches cliniques de Montréal
Montreal, Quebec, Canada, H2W 1R7
Sponsors and Collaborators
Institut de Recherches Cliniques de Montreal
Centre de Recherche du Centre Hospitalier de l'Université de Montréal
Investigators
Principal Investigator: Rémi Rabasa-Lhoret Institut de recherches cliniques de Montréal
  More Information

No publications provided

Responsible Party: Rémi Rabasa-Lhoret, Associate professor of Medicine, Institut de Recherches Cliniques de Montreal
ClinicalTrials.gov Identifier: NCT01828125     History of Changes
Other Study ID Numbers: Mini-doses glucagon
Study First Received: April 2, 2013
Last Updated: December 3, 2013
Health Authority: Canada: Ethics Review Committee

Keywords provided by Institut de Recherches Cliniques de Montreal:
Type 1 diabetes
Hypoglycemia
Glucagon
Hypoglycaemic hyperinsulinemic clamp

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Hypoglycemia
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Glucagon
Glucagon-Like Peptide 1
Hypoglycemic Agents
Gastrointestinal Agents
Therapeutic Uses
Pharmacologic Actions
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Incretins

ClinicalTrials.gov processed this record on August 01, 2014