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

Sponsor

Hvidovre University Hospital (Other)

Overall Status

Unknown status

CT.gov ID

NCT02232971

Collaborator

The Novo Nordic Foundation (Other), University of Copenhagen (Other)

Enrollment

Location

Arms

Duration (Months)

0.8

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Mellitus, Type 1	Drug: Glucagon Other: Isotonic saline solution	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

8 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Single (Participant)

Primary Purpose:

Basic Science

Official Title:

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

Study Start Date :

Sep 1, 2014

Actual Primary Completion Date :

Jan 1, 2015

Anticipated Study Completion Date :

Jul 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Maximum plasma glucose response [Plasma glucose measured every five minutes after administration]

Secondary Outcome Measures

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

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 [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.]
Visual analog scale
Adverse reaction: Headache [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.]
Visual Analog scale
Adverse Reaction: Vertigo [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.]
Visual analog scale
Adverse reaction: Nausea [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.]
Visual analog scale
Adverse reaction: Hunger [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.]
Visual analog scale
Plasma triglycerides [Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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