Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

Study Overview
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Brief Summary
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We hypothesized that short-term treatment with AP drugs induces insulin resistance through a mechanistic route that is independent of weight gain and that atypical drugs exert stronger effects than typical compounds in this respect. We therefore treated healthy non-obese men with olanzapine (atypical AP) or haloperidol (typical AP) for 8 days, and studied the impact of these interventions on glucose and lipid metabolism by hyperinsulinemic euglycemic clamp, isotope dilution technology and indirect calorimetry.

Official Title
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Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans

Conditions
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Insulin Resistance, Dyslipidemia

Intervention / Treatment
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* Drug: olanzapine
* Drug: Haloperidol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men, with and without a positive family history of schizophrenia. 20 kg/m2 < BMI < 26 kg/m2 Age 20-40 years Fasting plasma glucose < 6 mmo/L Exclusion Criteria: FPG > 6 mmol/L BMI > 26 kg/m2 Psychiatric disorders and/or use of antipsychotic or antidepressants drugs at present or in the past. Any significant chronic disease Renal, hepatic or endocrine disease Use of medication known to influence lipolysis and/or glucose metabolism Total cholesterol > 7mmol/L and/or triglycerides > 2 mmol/L Recent weight changes or attempts to loose weight (> 3 kg weight gain or loss, within the last 3 months) Difficulties to insert an intravenous catheter Smoking (current) Severe claustrophobia (ventilated hood) Recent blood donation (within the last 2 months) Recent participation in other research projects (within the last 3 months), participation in 2 or more projects in one year Extensive sporting activities (more than 10 hours of exercise per week)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Healthy men | Drug: olanzapine<br>* olanzapine 10 mg/day for 8 days<br>* Other names: Zyprexa;|
| Active Comparator: 2<br>Healthy men with a positive family anamneses of schizophrenia | Drug: olanzapine<br>* olanzapine 10 mg/day for 8 days<br>* Other names: Zyprexa;Drug: Haloperidol<br>* haloperidol 3 mg/day for 8 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine the effect of subchronic olanzapine and haloperidol treatment on HGO, whole body peripheral glucose disposal, fatty acid flux and fuel oxidation. |  | 8 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antipsychotics, Olanzapine, Haloperidol, Insulin resistance, Dyslipidemia