Pilot Study Investigating the Feasibility of Determining the Endogenous Glucose Production During a Hypoglycaemia
Condition: Type 1 Diabetes Mellitus
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Interventional
Phase: Phase 2

Summary: 
      Primary objective is to investigate the feasibility and stability of determining the
      endogenous glucose production during a hypoglycaemic clamp in type 1 diabetes mellitus
      subjects by a stable tracer to tracee ratio with an enrichment of 4% and a variation below
      +/-30%.

      Population: twenty type 1 diabetic subjects

      Study design: Single-center, open, non- randomized, pilot-study
    

Detailed description: 
      Each subject will participate on 3 Visits. The total study duration for each subject will be
      approximately one month.The trial can be divided into:

        -  Screening Visit (Visit 1)

        -  Hypoglycaemic clamp Visit (Visit 2)

        -  Follow up Visit (Visit 3)

      Screening Visit (Visit1):

      The subject will be asked to attend the screening visit fasting. The following data will be
      assessed and performed: informed consent signed and dated, inclusion and exclusion criteria
      for the study, a full medical history including current medication, physical examination and
      laboratory examination of blood/urine samples. For women in childbearing potential a urine
      pregnancy test will be performed.

      Hypoglycaemic Visit (Visit2):

      Each subject will be asked to attend the clinical unit at approximately 20:00 in the evening
      on day 1. Thereafter the subject will receive an insulin and glucose infusion intravenously
      in order to obtain a steady state of a PG level of 5.5 mmol/L overnight until approximately
      08:00 in the morning of day 2. At 05:00 hours D-[6,6-2H2] glucose (100 g/l) solution will be
      given i.v. as a primed (9.6 mg/kg/min) for one minute and a constant (0.08 mg/kg/min)
      infusion until the last blood sampling of the plasma glucose level of 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 Plasma Glucose 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, plasma glucose 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 level of 4.0 mmol/L and
      finally back to a level of 5.5 mmol/L for safety reasons. Blood sampling for measurement of
      plasma glucose, [6,6-2H2] glucose (labelled glucose),glucagon, vital signs, hypoglycaemic
      symptoms questionnaire and hypoglycaemic awareness will be performed at each plasma glucose
      plateau. The subject will be discharged from the clinic at day 2, or later if deemed
      necessary by the investigator.

      Follow up Visit (Visit 3):

      The subject will attend the Visit 3, 3 - 10 days after Visit 2. The following data will be
      assessed and performed: concomitant medication, including current diabetes treatment, adverse
      events, a full physical examination and laboratory examination of blood/urine samples. For
      women in childbearing potential a urine pregnancy test will be performed.
    

Intervention name(s): Insulin human
Intervention type(s): Drug
Intervention description(s): Induces hypoglycaemia
Other intervention name(s): Actrapid
Intervention MeSH terms: Insulin; Insulin, Globin Zinc
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: Endogenous glucose production; Type 1 diabetes mellitus; hypoglycaemic clamp; tracer to technique; pharmacodynamics; pharmacokinetics