Clinical trial NCT02232971: Treatment of Low Blood Sugar With Glucagon Among Patients With Type 1 Diabetes
Official title: Treatment of Hypoglycemia With Glucagon Among Patients With Type 1 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Diabetes Mellitus, Type 1
Keywords: glucagon
insulin pump
artificial pancreas
closed-loop
Lead sponsor: Hvidovre University Hospital
Sponsor class: OTHER
Collaborators: name: The Novo Nordic Foundation
name: University of Copenhagen
First posted: 2014-09-05
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: Maximum plasma glucose response
timeFrame: Plasma glucose measured every five minutes after administration
Secondary outcomes:
measure: Duration of hyperglycemic effect of glucagon
timeFrame: Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration
Other outcomes:
measure: Plasma Catecholamine
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma free fatty acids
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma Beta-Hydroxybutyric acid
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Plasma Glucagon
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Growth hormone
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Cortisol
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Serum Insulin (Novorapid)
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
measure: Adverse reaction: Stomach pain
timeFrame: 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.
measure: Adverse reaction: Headache
timeFrame: 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.
measure: Adverse Reaction: Vertigo
timeFrame: 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.
measure: Adverse reaction: Nausea
timeFrame: 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.
measure: Adverse reaction: Hunger
timeFrame: 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.
measure: Plasma triglycerides
timeFrame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration
Locations:
city: Hvidovre
country: Denmark
facility: Hvidovre University Hospital
Study officials:
affiliation: Hvidovre University Hospital
name: Ajenthen Ranjan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hvidovre University Hospital
name: Signe Schmidt, MD, PhD
role: STUDY_DIRECTOR
affiliation: Hvidovre University Hospital
name: Kirsten Nørgaard, MD, DMSc
role: STUDY_CHAIR
affiliation: Hvidovre University Hospital
name: Sten Madsbad, Prof, DMSc
role: STUDY_CHAIR
affiliation: University of Copenhagen
name: Jens J Holst, Prof, DMSc
role: STUDY_CHAIR
References: