Influence of Treatment With Olanzapine or Ziprasidone on Transcapillary Glucose Transport in Human Skeletal Muscle

NCT ID: NCT00297960

Last Updated: 2006-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-04-30

Brief 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.

Conditions

Healthy Male Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Blinding Strategy: NONE

Interventions

ziprasidone or olanzapine

Intervention Type: DRUG

hyperinsulinaemic euglycaemic clamp

Intervention Type: PROCEDURE

microdialysis (skeletal muscle)

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• Age between 18-55
• Healthy male volunteers
• No history of drug or alcohol abuse
• No regular nicotine consumption at time of enrollment
• Physical activity at least twice a week
• Body mass Index between 19-24 kg/m2
• Normal laboratory values
• Normotension (blood pressure less than 140/90)
• No past or present history of psychiatric disorder
• No family history of diabetes or obesity
• Written informed consent

Exclusion Criteria

• Use of medication within the last 14 days
• Consumption of alcohol within the last 5 days
• Family history of diabetes or obesity
• Past or present psychiatric disorder

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Principal Investigators

Siegfried Kasper, Prof. MD

Role: PRINCIPAL_INVESTIGATOR

Medical University Vienna, Department of General Psychiatry

Locations

Department of Clinical Pharmacology, Medical University Vienna

Vienna, , Austria

Countries

Austria

References

Newcomer JW, Haupt DW, Fucetola R, Melson AK, Schweiger JA, Cooper BP, Selke G. Abnormalities in glucose regulation during antipsychotic treatment of schizophrenia. Arch Gen Psychiatry. 2002 Apr;59(4):337-45. doi: 10.1001/archpsyc.59.4.337.

Reference Type: BACKGROUND

PMID: 11926934 (View on PubMed)

Rosdahl H, Lind L, Millgard J, Lithell H, Ungerstedt U, Henriksson J. Effect of physiological hyperinsulinemia on blood flow and interstitial glucose concentration in human skeletal muscle and adipose tissue studied by microdialysis. Diabetes. 1998 Aug;47(8):1296-301. doi: 10.2337/diab.47.8.1296.

Reference Type: BACKGROUND

PMID: 9703331 (View on PubMed)

Muller M, Holmang A, Andersson OK, Eichler HG, Lonnroth P. Measurement of interstitial muscle glucose and lactate concentrations during an oral glucose tolerance test. Am J Physiol. 1996 Dec;271(6 Pt 1):E1003-7. doi: 10.1152/ajpendo.1996.271.6.E1003.

Reference Type: BACKGROUND

PMID: 8997218 (View on PubMed)

Other Identifiers

EUDRACT Nr.: 2004-002147-27

Identifier Type: -

Identifier Source: secondary_id

olanz/zipra

Identifier Type: -

Identifier Source: org_study_id