Diabetes Mellitus, Type 1
Conditions
Keywords
glucagon, insulin pump, artificial pancreas, closed-loop
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.
Interventions
DRUGGlucagon
Glucagon is given in three different doses according to three research days.
Placebo
Sponsors
The Novo Nordic Foundation
University of Copenhagen
Hvidovre University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum plasma glucose response | Plasma glucose measured every five minutes after administration |
Secondary
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Plasma Catecholamine | Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration | — |
| 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 | — |
| 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 |
| Plasma free fatty acids | Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration | — |
Countries
Denmark
Outcome results
None listed