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

• ClinicalTrials.gov Identifier: NCT02232971
• Recruitment Status: Unknown
• First Posted: September 5, 2014
• Last Update Posted: March 25, 2015
• Sponsor: Hvidovre University Hospital
• Collaborators: The Novo Nordic Foundation; University of Copenhagen
• Information provided by (Responsible Party): Ajenthen Ranjan, Hvidovre University Hospital

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 (Clinical Trial)
• Estimated 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: September 2014
• Actual Primary Completion Date: January 2015
• Estimated Study Completion Date: July 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 :

1. Maximum plasma glucose response [ Time Frame: Plasma glucose measured every five minutes after administration ]

Secondary Outcome Measures :

1. Duration of hyperglycemic effect of glucagon [ Time Frame: Plasma glucose is measured every five minutes. Time period is two -three hours after glucagon administration ]

Other Outcome Measures:

1. Plasma Catecholamine [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
2. Plasma free fatty acids [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
3. Plasma Beta-Hydroxybutyric acid [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
4. Plasma Glucagon [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
5. Serum Growth hormone [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
6. Serum Cortisol [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
7. Serum Insulin (Novorapid) [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]
8. Adverse reaction: Stomach pain [ Time Frame: 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
9. Adverse reaction: Headache [ Time Frame: 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
10. Adverse Reaction: Vertigo [ Time Frame: 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
11. Adverse reaction: Nausea [ Time Frame: 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
12. Adverse reaction: Hunger [ Time Frame: 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
13. Plasma triglycerides [ Time Frame: Measured at 0, 5, 10, 15, 30, 45, 60, 90, 120,180, 240 minutes after glucagon administration ]

Eligibility Criteria

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

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

Contacts and Locations

Locations

Denmark

Hvidovre University Hospital

Hvidovre, Denmark, 2650

Sponsors and Collaborators

Hvidovre University Hospital

The Novo Nordic Foundation

University of Copenhagen

Investigators

• Principal Investigator: Ajenthen Ranjan, MD; Hvidovre University Hospital
• Study Director: Signe Schmidt, MD, PhD; Hvidovre University Hospital
• Study Chair: Kirsten Nørgaard, MD, DMSc; Hvidovre University Hospital
• Study Chair: Sten Madsbad, Prof, DMSc; Hvidovre University Hospital
• Study Chair: Jens J Holst, Prof, DMSc; University of Copenhagen

More Information

Additional Information:

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

• Responsible Party: Ajenthen Ranjan, MD, PhD student, Hvidovre University Hospital
• ClinicalTrials.gov Identifier: NCT02232971
• Other Study ID Numbers: GluST1_2014; 2014-002267-15 ( EudraCT Number ); H-1-2014-041 ( Other Identifier: The National Committee on Health Research Ethics )
• First Posted: September 5, 2014
• Last Update Posted: March 25, 2015
• Last Verified: March 2015

Keywords provided by Ajenthen Ranjan, Hvidovre University Hospital:

glucagon; insulin pump; artificial pancreas; closed-loop

Additional relevant MeSH terms:

Diabetes Mellitus; Diabetes Mellitus, Type 1; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases; Glucagon; Gastrointestinal Agents; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs