Treatment of Low Blood Sugar With Glucagon Among Patients With Type 1 Diabetes (GluST1)

Treatment of Hypoglycemia With Glucagon Among Patients With Type 1 Diabetes Mellitus

Background: Patients with type 1 diabetes (T1D) need a lifelong supply of external insulin and are advised to aim for near-normalization of blood glucose levels through intensive insulin therapy. We propose a new approach for achieving treatment goals in T1D: the combined use of insulin and glucagon, i.e. dual-hormone treatment.Only recently the prospect of treating patients with soluble glucagon has arisen and thus studies of low dose glucagon treatment of mild hypoglycemia are needed to determine whether there is clinical rationale for dual-hormone treatment of T1D.

Aim: The purpose of this clinical study is to investigate the glycemic response to subcutaneous glucagon administration during mild hypoglycemia in T1D patients treated with insulin pump. Different glucagon doses are applied to determine the most appropriate dose for future dual-hormone treatment of T1D.

Methods: A clinical, randomized, single blinded, crossover study will be conducted. Eight T1D patients treated with insulin pump are studied on four days. All patients are in good metabolic control (HbA1c < 7.5%), C-peptide negative and with hypoglycemia awareness. On each study day, hypoglycemia is induced with subcutaneously insulin and afterward treated with a single subcutaneous dose of glucagon. The study procedures are identical on all days except from the administered dose of glucagon (day 1: placebo, day 2: 100 ug, day 3: 200 ug, day 4: 300 ug). All patients are blinded for the glucagon dose and carry out the four days in random order.

Endpoints: The present study focuses primarily on the dose related plasma glucose response of glucagon; secondary on the duration of the hyperglycemic effect of glucagon and tertiary the glucagon effect on catecholamine, cortisol, growth hormone, free fatty acids and triglycerides.

The study will be conducted from august 2014.

Study Overview

• Status: Unknown
• Conditions: Diabetes Mellitus, Type 1
• Intervention / Treatment: Other: Isotonic saline solution; Drug: Glucagon

• Study Type: Interventional
• Enrollment (Anticipated): 8
• Phase: Phase 4

Contacts and Locations

Study Locations

• Denmark
  • Hvidovre, Denmark, 2650
    • Hvidovre University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females aged 18-65 years
• Diagnosed with type 1 diabetes > 3 years
• HbA1c < 58 mmol/mol
• No appearance of autonome neuropathy
• Body mass index (BMI) between 20-25 kg/m2
• Remained hypoglycemic awareness
• Insulin pump treatment > 1 year

Exclusion Criteria:

• Allergic to glucagon or lactose
• Pregnancy, breast-feeding, intention of becoming pregnant, or not using adequate contraception
• Any disease or condition which would interfere with the subject's safety
• Use of a medication that significantly impacts glucose metabolism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Isotonic Saline	Other: Isotonic saline solution; Placebo; Other Names: Natriumklorid isotonisk "SAD"; D.sp.no. 6733; Amgros I/S; Dampfærgevej 22; Postbox 2593; 2100 København Ø
Experimental: Glucagon 0.1 mg; GlucaGen(r) 0.1 mg administration	Drug: Glucagon; Glucagon is given in three different doses according to three research days.; Other Names: GlucaGen (r); Disp. no. 2514; Novo Nordisk A/S; Novo Allé; 2880 Bagsværd
Experimental: Glucagon 0.2 mg; GlucaGen(r) 0.2 mg administration	Drug: Glucagon; Glucagon is given in three different doses according to three research days.; Other Names: GlucaGen (r); Disp. no. 2514; Novo Nordisk A/S; Novo Allé; 2880 Bagsværd
Experimental: Glucagon 0.3 mg; GlucaGen(r) 0.3 mg administration	Drug: Glucagon; Glucagon is given in three different doses according to three research days.; Other Names: GlucaGen (r); Disp. no. 2514; Novo Nordisk A/S; Novo Allé; 2880 Bagsværd

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum plasma glucose response	Plasma glucose measured every five minutes after administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of hyperglycemic effect of glucagon	Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Catecholamine		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Plasma free fatty acids		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Plasma Beta-Hydroxybutyric acid		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Plasma Glucagon		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Serum Growth hormone		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Serum Cortisol		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Serum Insulin (Novorapid)		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Adverse reaction: Stomach pain	Visual analog scale	One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
Adverse reaction: Headache	Visual Analog scale	One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
Adverse Reaction: Vertigo	Visual analog scale	One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
Adverse reaction: Nausea	Visual analog scale	One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
Adverse reaction: Hunger	Visual analog scale	One time before and after insulin administration. One time before glucagon administration. After glucagon administration at T=15 min., T=60 min., T=120 min., T=240 min.
Plasma triglycerides		Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration

Collaborators and Investigators

• Sponsor: Hvidovre University Hospital
• Collaborators: University of Copenhagen; The Novo Nordic Foundation
• Investigators: Principal Investigator: Ajenthen Ranjan, MD, Hvidovre University Hospital; Study Director: Signe Schmidt, MD, PhD, Hvidovre University Hospital; Study Chair: Sten Madsbad, Prof, DMSc, Hvidovre University Hospital; Study Chair: Jens J Holst, Prof, DMSc, University of Copenhagen

Publications and helpful links

Helpful Links

• DiaCon group focuses on developing new technologies for treatment of type 1 diabetes

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): January 1, 2015
• Study Completion (Anticipated): July 1, 2015

Study Registration Dates

• First Submitted: August 29, 2014
• First Submitted That Met QC Criteria: September 3, 2014
• First Posted (Estimate): September 5, 2014

Study Record Updates

• Last Update Posted (Estimate): March 25, 2015
• Last Update Submitted That Met QC Criteria: March 24, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: glucagon; insulin pump; artificial pancreas; closed-loop
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Physiological Effects of Drugs; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Glucagon
• Other Study ID Numbers: GluST1_2014; 2014-002267-15 (EudraCT Number); H-1-2014-041 (Other Identifier: The National Committee on Health Research Ethics)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No