NCT02408705

Investigating the Effect of Liraglutide on the Endogenous Glucose Production During in Tye 1 Diabetes Subjects

A Randomized, Double Blind, Two-period Cross-over Trial Investigating the Effect of Liraglutide as Add on to Intensive Insulin Treatment on the Endogenous Glucose Production in Subjects With C-peptide Positive Type 1 Diabetes Mellitus

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 14 (actual)
• Sponsor: Medical University of Graz · Academic / Other
• Sex: All
• Age: 18 Years – 64 Years
• Healthy volunteers: Not accepted

Summary

Each subject will be allocated to 2 periods of 3 months of once daily dosing with either liraglutide (1.2 mg) or placebo treatment (in random sequence) as add on to usual intensive insulin treatment. Wash-out period between treatments will be 1 month. The trial can be divided into the following periods: * Screening * Treatment period 1 * Washout period * Treatment period 2 * Follow up Visit Mixed Meal Tolerance Test (MMTT) enriched with paracetamol: At the beginning and end of each period a MMTT (Fortimel complete) enriched with paracetamol will be performed to assess the remaining beta-cell function via obtained maximal plasma C-peptide levels as well as the gastric emptying. Experimental / Hypoglycaemic clamp : At the end of each period (Visit 8, 15) a hypoglycaemic clamp will be performed. After the subject completed the MMTT on day 1, the subject will stay in the clinical unit to prepare for the hypoglycaemic clamp with an variable insulin infusion intravenously in order to obtain a steady state of a plasma glucose (PG) level of 5.5 mmol/L overnight until approximately 08:00. At 05:00 hours 10%-\[6,6-2H2\] glucose solution will be given i.v. as a primed (9.6mg/kg/min) for one minute and a constant (0.08 mg/kg/min) infusion until the last blood sampling of the plateau 4.0 mmol/L will be performed. At 08:00 hours in the morning at day 2, insulin infusion will be increased to 1.5 mU/kg/min for each subject and the PG will be kept at a plateau of 5.5 mmol/L by a controlled variable intravenous infusion of glucose (10% glucose enriched with 4mg \[6,6-2H2\] glucose /ml) for one hour. Afterwards, PG is allowed to fall to a plateau of 3.5 mmol/L, then to a nadir of 2.5 mmol/L, then to a blood glucose of 4.0 mmol/L and finally back to a level of 5.5 mmol/L for safety reasons. Blood sampling for measurement of \[6,6-2H2\] glucose, glucagon, insulin, counterregulatory hormones, lactate, free fatty acids, glycerol, vital signs, hypoglycaemic symptoms questionnaire and hypoglycaemic awareness will be performed at each PG plateau.

Conditions

• Type 1 Diabetes Mellitus

Interventions

Type	Name	Description
DRUG	Liraglutide	They are receiving liraglutide for 3 months. Dose escalation: 0.3 mg - 0.6mg - 0.9mg - 1.2mg (over 4 weeks)
DRUG	Placebo	They are receiving placebo for 3 months. Dose escalation: 0.3 mg - 0.6mg - 0.9mg - 1.2mg (over 4 weeks)
DRUG	Mixed Meal Tolerance Test with paracetamol	At the beginning and end of each period (Visit 2a, 8, 9a, 15) a Mixed Meal Tolerance Test enriched paracetamol will be performed.

Timeline

• Start date: 2015-01-01
• Primary completion: 2016-05-01
• Completion: 2016-05-01
• First posted: 2015-04-03
• Last updated: 2016-09-12

Locations

1 site across 1 country: Austria