Investigating the Effect of Liraglutide on the Endogenous Glucose Production During in Tye 1 Diabetes Subjects
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

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.
    


Intervention name(s): Liraglutide; Placebo; Mixed Meal Tolerance Test with paracetamol
Intervention type(s): Drug; Drug; Drug
Intervention description(s): They are receiving liraglutide for 3 months. Dose escalation: 0.3 mg - 0.6mg - 0.9mg - 1.2mg (over 4 weeks); They are receiving placebo for 3 months. Dose escalation: 0.3 mg - 0.6mg - 0.9mg - 1.2mg (over 4 weeks); At the beginning and end of each period (Visit 2a, 8, 9a, 15) a Mixed Meal Tolerance Test enriched paracetamol will be performed.
Other intervention name(s): Victoza; MMTT
Intervention MeSH terms: Acetaminophen; Liraglutide
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Basic Science
Keywords: Endogenous Glucose Production; Hypoglycemic clamp; Tracer to Tracee Technique; Type 1 diabetes mellitus