Influence of Treatment With Olanzapine or Ziprasidone on Transcapillary Glucose Transport in Human Skeletal Muscle
Condition: Healthy Male Volunteers
Study type: Interventional
Phase: Phase 4

Summary: 
      Healthy volunteers will undergo euglycaemic hyperinsulinaemic clamp and microdialysis before
      and after administration of 10mg olanzapine or 80mg ziprasidone during 10 days.
    

Detailed description: 
      Background:

      The efficacy of atypical antipsychotics, such as olanzapine, clozapine, risperidone,
      quetiapine and ziprasidone in treating a broad spectrum of symptoms in schizophrenia as well
      as their lower likelihood of extrapyramidal symptoms have led to an increased use of these
      substances. However there is an ongoing debate whether treatment with atypical antipsychotics
      is associated with a higher risk for metabolic abnormalities. The FDA stated in 2003 that all
      atypical antipsychotics increase the risk for glucose abnormalities. For olanzapine many, but
      not all studies report an increased risk for the development of metabolic abnormalities, such
      as glucose intolerance, insulin-resistance and consequentially NIDDM
      (Non-Insulin-Dependent-Diabetes Mellitus). Ziprasidone on the other hand seems to be
      associated with a more favorable metabolic safety profile.Glucose intolerance and insulin
      resistance being risk factors for the development of NIDDM and cardiovascular disease, the
      exact determination of putative effects of atypical antipsychotics on insulin sensitivity and
      resistance is of great need. An innovative technique, microdialysis, allows for the
      measurement of various analytes in the interstitial space, i.e. to assess insulin sensitivity
      directly at the responsible compartment, which is the human skeletal muscle. With the use of
      microdialysis it is possible to determine the arterial to interstitial gradient, a suitable
      marker for plasma glucose extraction of peripheral tissue, and thus detect insulin resistance
      directly at the site of insulin action.

      Aim of the study:

      To compare the effects of treatment with the atypical antipsychotics olanzapine and
      ziprasidone in steady-state conditions on the arterial to interstitial skeletal muscle
      gradient for glucose in human skeletal muscle during euglycaemic hyperinsulinaemic clamp
      conditions in male healthy volunteers.

      Study design:

      Open, randomized, mono-center study.

      Materials and methods:

      Healthy volunteers will undergo euglycaemic hyperinsulinaemic clamp and microdialysis before
      and after administration of 10mg olanzapine or 80mg ziprasidone during 10 days.

      Study population:

      15 healthy volunteers will participate in each arm of the study, summing up to a total of 30
      participants.

      Main outcome variable:

      The arterial to interstitial skeletal muscle glucose gradient before and during euglycaemic
      hyperinsulinaemic clamp conditions, before and after administration of 10mg olanzapine or
      80mg ziprasidone under steady-state conditions.
    

Intervention name(s): ziprasidone or olanzapine; hyperinsulinaemic euglycaemic clamp; microdialysis (skeletal muscle)
Intervention type(s): Drug; Procedure; Procedure
Intervention MeSH terms: Olanzapine; Ziprasidone
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)